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Mukul Das

INDIAN INSTITUTE OF TOXICOLOGY RESEARCH, Area Coordinator, Food, Drug & Chemical Toxicology Group, Ex- Chief Scientist

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Phone: 9335041295
Address: Ex- Chief Scientist
CSIR- Indian Institute of Toxicology Research,
B 33, Mehrotra Apts, Apt # 305, Opp Toys & Joys School, Sector J, Aliganj, Lucknow 226024

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Cabeza-Herrera E.A.

Universidad de Pamplona

Mohammed Wasim Siddiqui

Bihar Agricultural University

Maarire Goodall

University of Otago

Benha University

Kamla Kant Shukla

All India Institute of Medical Sciences, Jodhpur

University of Mumbai

William H Bisson

Oregon Health & Science University

The University of Western Australia

University of East London

Gwen Robbins Schug

University of North Carolina at Greensboro

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Papers by Mukul Das

Assessment of the effectiveness of open defecation free system on the incidence of faecal contamination on environment through microbial source tracking

The aim of this study was to assess the effectiveness of open defecation free (ODF) system on the... more The aim of this study was to assess the effectiveness of open defecation free (ODF) system on the incidence of faecal contamination on environment (water, soil and food mediums). The magnitude of contamination of environmental medium of ODF and non-open defecation free (n-ODF) villages by faecal indicator bacteria (FIB) in three states of India, was investigated. The FIB positive samples were further processed to determine the source of faecal contamination using Bacteroidale molecular markers for human (HuBac). The matrix of relative risk (RR) due to FIB and HuBaC contamination was developed to assess the effectiveness of ODF interventions. When compared to ODF villages, the RR of faecal contamination in n-ODF villages was estimated 11.25 times more likely in groundwater, 2.68 times more likely in household storage drinking water, 2.71 times more likely in piped water supplies, 1.13 times more likely in soil and 1.48 times more likely in food. The RR of faecal contamination traceab...

Species differences between rat and human in vitro metabolite profile, in vivo predicted clearance, CYP450 inhibition and CYP450 isoforms that metabolize benzanthrone: Implications in risk assessment

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, Jan 7, 2017

Benzanthrone (BNZ) is a polycyclic aromatic hydrocarbon found in industrial effluent causing skin... more Benzanthrone (BNZ) is a polycyclic aromatic hydrocarbon found in industrial effluent causing skin, respiratory, gastrointestinal, genitourinary, nervous and hemopoietic toxicity. While its toxicity has been well studied, its metabolism in humans has not been investigated. The aim of this study was to characterize species differences in the in vitro metabolism of BNZ in rat and human liver microsomes and to identify the CYP isoforms involved in its metabolism. Upon incubation in liver microsomes, BNZ was found to be a direct substrate of phase I metabolism in both rat and human, undergoing oxidation and reduction. The Km in rat, 11.62 ± 1.49 μM, was two-fold higher than humans (5.97 ± 0.83 μM) suggesting higher affinity for human CYPs. Further, incubation with human rCYPs, BNZ was found to be substrate of multiple CYPs. The predicted in vivo hepatic clearance was 63.55 and 18.91 mL/min/kg in rat and human, respectively, indicating BNZ to be a high clearance compound. BNZ was found to...

Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Clinical and Translational Allergy, 2017

Introduction: Incidence of anaphylaxis is increasing. Data regarding anaphylaxis mortality are li... more Introduction: Incidence of anaphylaxis is increasing. Data regarding anaphylaxis mortality are limited, but conflicting. Our objective was to document anaphylaxis mortality rate (deaths per million population), time trends and specificities according to triggers (iatrogenic, venom, food, unknown), age groups, sex and geographical regions (North and South) in France, between 1979 and 2011. Methods: Data were obtained (1) from database of the National Mortality Center (CEPIDC) to collect cases in which anaphylaxis was included as a cause of death, sex, age, and geographic region of death, (2) from the database of the National Institute for Economical and Statistical studies (INSEE) to define the referent populations. We used a multivariable log-linear Poisson regression model to assess the impact of time period, age, sex and geographic region on anaphylaxis deaths. Results: During the period study, 1603 deaths were collected: 1564 in adults and 39 in children (age <18 year). The overall prevalence of anaphylaxis fatalities was 0.84 per million population (95% IC 0.80-0.88), ranging from 0.08 per million (95% IC 0.05-0.10) in pediatric population to 1.12 per million (95% CI 1.06 to 1.17) in adult population. Annual percentage change for case fatality rate was −2.0% (95% CI −2.5 to −1.5; p < 10 −4) indicating a decrease in case fatality rate during the study period. Anaphylaxis fatality rate was higher in men (1.08 per million [95% IC 1.00 1.16] than women (0.86 per million [95% IC 0.80-0.92]) (p < 10 −4). Triggers of anaphylaxis fatalities were iatrogenic (63%), mostly drugs, venom (14%) and food (0.6%). Unspecified anaphylaxis was frequent (23%). The highest rate was in persons aged >70 years (3.50 per million population per year [95% IC 3.25-3.76]) and the lowest in the pediatric population (p < 10 −4). Only venom-induced mortality rate was higher in South of France (0.16 per million [95% IC 0.13-0.19]) compared with the North (0.11 per million [95% IC 0.09-0.13]) (p = 0.004). Only 8 food-induced fatalities were recorded (age <35 years in 7 cases). Conclusion: Overall anaphylaxis mortality rate is decreasing over the three last decades in France. We confirm that iatrogenic causes are the most frequent causes. Older age and male sex are risk factors of fatal anaphylaxis of any cause except for food-induced anaphylaxis.

Hepatomyoencephalopathy in Malkangiri district of Odisha, India

Current Science, 2017

During September through November 2016, some 100 children died due to acute brain disease in Malk... more During September through November 2016, some 100 children died due to acute brain disease in Malkangiri district, southern Odisha, India. Most deaths were at first attributed to Japanese encephalitis (JE) due to the following reasons: JE had been reported in Malkangiri district in previous years and diagnostic test for JE was positive in a few children in 2016; JE season is September through November; the vector mosquitoes and amplifying hosts, namely pigs, are prevalent in Malkangiri district. However, a number of cases turned out negative for JE test. Therefore, in the last week of October, the Department of Health, Government of Odisha, constituted a team to investigate the cases of non-JE acute brain disease with high mortality. We conducted a rapid review and investigations during the first two weeks of November. Two of us (G.A. and M.M.P.) had visited Malkangiri district during October when the clinical pattern of non-JE cases was found to be stereotyped: relatively abrupt ons...

Argemone oil, an edible oil adulterant, induces systemic immunosuppression in balb/c mice in an oral 28 days repeated dose toxicity study

Chemico-biological interactions, Jan 12, 2018

Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition call... more Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2). At the functional level, AO exposure significantly abrogated the mixed lymphocyte reaction and mitogen-stimulated lymphoproliferative activity of T and B cells, which is reflective of profound lymphocyte dysfunction upon antigen exposure. In concordance with the los...

CSIR-Indian Institute of Toxicology Research, Lucknow

Current Science, 2015

CSIR-Indian Institute of Toxicology Research (IITR), Lucknow, established on 4 November 1965, is ... more CSIR-Indian Institute of Toxicology Research (IITR), Lucknow, established on 4 November 1965, is one of the pioneer institutions dealing with toxicology research in the Asia-Pacific region. IITR is the only laboratory in the CSIR family to be awarded the Good Laboratory Practice certification. The five decades of expertise and knowledge base in toxicology research have empowered the Institute to conduct studies in the following niche areas: (i) Food, drug and chemical toxicology, (ii) nanotherapeutics and nanomaterial toxicology, (iii) systems toxicology and health risk assessment, (iv) environmental toxicology, and (v) regulatory toxicology. The highlights of some of the scientific achievements for the year 2014 are described in this article.

Fatty Acid Composition Including<i>Trans</i>-Fatty Acids in Edible Oils and Fats: Probable Intake in Indian Population

Journal of Food Science, Sep 5, 2012

: The susceptibility of trans‐fat to the human health risk prompted the Food and Agriculture Org... more : The susceptibility of trans‐fat to the human health risk prompted the Food and Agriculture Organization (FAO) and World Health Organization (WHO) to prepare regulations or compulsory claims for trans‐fatty acids (TFA) in edible oils and fats. In this study, analysis of fatty acid composition and TFA content in edible oils and fats along with the possible intake of trans‐fat in Indian population was carried out. The analysis was carried out as per the Assn. of Official Analytical Chemists (AOAC) methodology and the results were statistically analyzed. The average TFA content in nonrefined mustard and refined soybean oils exceeded by 1.16‐ to 1.64‐fold as compared to the Denmark limit of 2% TFA in fats and oils destined for human consumption. In branded/nonbranded butter and butter oil samples, average TFA limit exceeded by 4.2‐ to 9.5‐fold whereas hydrogenated vegetable oil (HVO) samples exceeded the limit by 9.8‐fold, when compared to Denmark standards. The probable TFA intake per day through different oils in Indian population were found to be less than WHO recommendation. However Punjab having highest consumption of HVO (–15 g/d) showed 1.09‐fold higher TFA intake than the WHO recommendation, which is alarming and may be one of the factors for high cardiovascular disease mortality rate that needs further elucidation. Thus there is a need to prescribe TFA limit for edible oil, butter, and butter oil in India and to reduce the already proposed TFA levels in HVO to safeguard the health of consumers.Practical Application: The probable daily intake of trans‐fatty acid (TFA) especially through hydrogenated vegetable oil (HVO) was assessed. In absence of any specification for TFA and fatty acid composition for edible oils, butter, and butter samples, a pressing need was felt to prescribe TFA limit in India. The study indicates that TFA intake through HVO consumption is higher in States like Punjab than the recommended daily intake prescribed by WHO. Hence, strategies should be adopted to either decrease the consumption of HVO or to modify the industrial processing method of HVO with less content of TFA to safeguard the health of consumers.

Detection of polycyclic aromatic hydrocarbons in commonly consumed edible oils and their likely intake in the Indian population

Journal of the American Oil Chemists' Society, Dec 1, 2004

Edible oils such as coconut, groundnut, hydrogenated vegetable, linseed, mustard, olive, palm, re... more Edible oils such as coconut, groundnut, hydrogenated vegetable, linseed, mustard, olive, palm, refined vegetable, rice bran, safflower, sesame, soybean, and sunflower were analyzed for the presence of light and heavy polycyclic aromatic hydrocarbon (PAH) residues using liquid-liquid extraction, cleanup on a silica gel column, and resolution and determination by HPLC using a fluorescence detector. Ten PAH viz. acenaphthene, anthracene, benzo(a)pyrene, benzo(e)pyrene, benz(ghi)perylene, chrysene, coronene, cyclopenta(def)phenanthrene, phenanthrene, and pyrene were monitored. Analysis of 296 oil samples showed that 88.5% (262) samples were contaminated with different PAH. Of 262 contaminated edible oil samples, 66.4% of the samples showed PAH content of more than the 25 µg/kg recommended by the German Society for Fat Science. The total PAH content was highest in virgin olive oil (624 µg/kg) and lowest in refined vegetable oils (40.2 µg/kg). The maximum content (265 µg/kg) of heavy PAH was found in olive oil and the minimum (4.6 µg/kg) in rice bran oil. Phenanthrene was present in 58.3% of the oil samples analyzed, followed by anthracene (53%). Among the heavy PAH, benzo(e)pyrene was observed in 31.2% of the samples followed by benzo(a)pyrene (25.5%). The intake of PAH was highest through olive oil (20.8 µg/day) followed by soybean oil (5.0 µg/day) and lowest through refined vegetable oil (1.3 µg/day). Based on these monitoring studies, international and national guidelines for permissible levels of PAH can be prepared so as to restrict the intake of these toxic contaminants.

A Simple Method for Simultaneous Determination of Basic Dyes Encountered in Food Preparations by Reversed-Phase HPLC

Journal of AOAC International, Nov 1, 2011

The present method utilizes a simple pretreatment step, cleanup on polyamide SPE cartridges, and ... more The present method utilizes a simple pretreatment step, cleanup on polyamide SPE cartridges, and HPLC resolution on reversedphase C18 for the detection of the three basic nonpermitted dyes encountered in food matrixes. Polyamide cartridges were chosen because both acidic and basic dyes can be cleaned up due to their amphoteric nature. Analysis was performed on a reversed-phase C18 µ-Bondapak column using the isocratic mixture of acetonitrile-sodium acetate with a flow rate of 1.5 mL/min and a programmable λ max specific visible detection to monitor colors, achieving higher sensitivity and expanded scope to test multicolor blends. All the colors showed linearity with the regression coefficient, from 0.9983 to 0.9995. The LOD and LOQ ranged between 0.107 and 0.754 mg/L and 0.371 and 2.27 mg/L or mg/kg, respectively. The intraday and interday precision gave good RSDs, and percentage recoveries in different food matrixes ranged from 75 to 96.5%. The study demonstrates that the use of a combination of a simple SPE cleanup and HPLC resolution with UV-Vis end point detection was successful in screening the presence of these three basic nonpermitted dyes individually or in blend, in a variety of food matrixes.

Correction: Topical Application of Ochratoxin A Causes DNA Damage and Tumor Initiation in Mouse Skin

PLOS ONE, Nov 26, 2018

Incorrect images were used for the Control and OTA (80μg) panels of Fig 1D of this article [1], w... more Incorrect images were used for the Control and OTA (80μg) panels of Fig 1D of this article [1], which are duplicates of the Control and CTN (48h) panels, respectively, in Fig 2B of the following article previously published in the journal Toxicological Sciences: Citrinin-Generated Reactive Oxygen Species Cause Cell Cycle Arrest Leading to Apoptosis via the Intrinsic Mitochondrial Pathway in Mouse Skin [2]

Simultaneous Determination of Acetaminophen and Synthetic Color(s) by Derivative Spectroscopy in Syrup Formulations and Validation by HPLC: Exposure Risk of Colors to Children

Aaps Pharmscitech, Nov 6, 2014

Color additives are used in pediatric syrup formulations as an excipient; though not prerequisite... more Color additives are used in pediatric syrup formulations as an excipient; though not prerequisite, but pediatric syrup formulations are normally colored. An attempt has been made to measure simultaneously the single drug, acetaminophen (AT), along with the colors, carmoisine (CA), erythrosine (ET), and sunset yellow FCF (SSY) added in it by three derivative spectroscopy methods namely, 1st order, ratio, and differential derivative methods. Moreover, evaluation has been made for the exposure assessment of the colors added as excipient because some colors have been reported to cause allergic reactions and hypersensitivity in children. The present methods provide simple, accurate, and reproducible quantitative determination of the drug, AT, along with the color in synthetic mixtures and commercial drug formulations without any interference. The limit of detection varied from 0.0001-0.31 μg/ml while limit of quantification ranged from 0.002-1.04 μg/ml in all the three methods. The calibration curve of all the three derivative methods exhibited good linear relationship with excellent regression coefficients (0.9986-1.000). Both intra-day and inter-day precisions showed %RSD value less than 2% while the percentage recovery was found between 96.8-103.8%. The sensitivity of the proposed methods is almost comparable to HPLC and thus, can be used for determination of drug AT, and color simultaneously in pharmaceutical formulation on routine basis. The present methods also showed that colors like SSY and ET are saturating more than 50% of acceptable daily intake (ADI) value which is alarming and needs to be considered for modification by regulatory authorities to safeguard the health of children.

Intake pattern of synthetic colours by different age and socio-economic consumer groups of Lucknow, India

International Journal of Food, Nutrition and Public Health, 2010

Exposure assessment of synthetic food colours in different age and socioeconomic groups of consum... more Exposure assessment of synthetic food colours in different age and socioeconomic groups of consumers revealed that on average intake of food commodities, only Erythrosine exceeded the acceptable daily intake (ADI) limit in the 1–10 and 11–20 years age groups through sugar toys on both normal (19–115%) and festive occasions (8–236%). However, on maximum likely intake of foods, Sunset Yellow FCF, Tartrazine, Carmoisine and Erythrosine were found to exceed the ADI limits several times, ranging between 14–1, 138% in 1–10 year and 45–765% in 11–20 year age subjects. Among foods predominantly consumed by children, crushed ice, ice-candy, ice cream, beverages, sweets and sugar toys were identified as the culprits leading to excessive intake of colours. The permitted levels of colours allowed in food commodities, need to be reviewed periodically and should be governed by technological necessity and the consumption profiles of the food commodity so that colours do not cross the prescribed ADI-based safety umbrella and pose a threat to vulnerable populations.

Toxicity of Naturally Occurring Anthraquinones

Advances in Molecular Toxicology, 2017

Abstract Among the vast array of secondary metabolites produced by plants, anthraquinones (AQs) a... more Abstract Among the vast array of secondary metabolites produced by plants, anthraquinones (AQs) are the group of compounds produced by different plants of various families such as Polygonaceae, Rhamnaceae, Rubiaceae, Fabaceae, Xanthorrhoeaceae, Leguminosae, and Liliacae. Owing to their biological and chemical diversity, AQs have wide industrial applications in food, pharmaceutical, and paper industries. Despite their diverse application, anthraquinones have been reported to be toxic to experimental animals. However, very little is known about their toxicity on the human population. In this chapter, the metabolic routes for the biosynthesis of AQs in plants have been described. Efforts have been focused on the profile of AQs present in different plant species and their toxic effects on the various animal models and in humans.

Sustained Release Tablets of Sorafenib-Silibinin Combinations for the Treatment of Hepatocellular Carcinoma

International Journal of Applied Pharmaceutics, 2018

Objective: The aim of this study was to develop polymer coated sustained release tablet using sor... more Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma.Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation.Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommenda...

Corrigendum to “A novel function of TLR4 in mediating the immunomodulatory effect of Benzanthrone, an environmental pollutant” [Toxicol. Lett. 276 (May) (2017) 69–84]

Toxicology Letters, 2019

Simple Extraction Cum RP-HPLC Method for Estimation of Nanotized Quercetin in Serum and Tissues of Mice

Pharmaceutical Chemistry Journal, 2018

In recent years, several studies have focused on antioxidant, anti-inflammatory, and anti-cancer ... more In recent years, several studies have focused on antioxidant, anti-inflammatory, and anti-cancer activities of quercetin (3,3¢,4¢,5,-pentahydroxyflavone). The nanotization of quercetin was shown to enhance its therapeutic efficacy due to smaller particle size. In the present study, an additional step was added to simple extraction cum RP-HPLC method for the quantification of nanotized quercetin (nQ) in biological samples to understand the pharmacokinetics and biodistribution of nQ following intravenous administration. The proposed method involves extraction of nQ from blood serum and tissues of mice with 2N HCl in comparison to well-known DMSO:MeOH mix method. The HCl extraction was found to be 2-3 times more efficient than DMSO:MeOH mix method. Results showed that the amount of nQ at various time intervals in the serum and tissues was 2-3 fold greater for HCl extraction than for DMSO:MeOH mix method, suggesting that HCl extraction must take into account nQ bound with protein. The reversed-phase HPLC was used for nQ detection, which showed the nQ retention time of 3.2 min. The limit of detection of nQ in blood serum was found to be 0.1 mg/mL. The proposed method was also validated in terms of linearity, precision, and accuracy.

Fungal mediated biotransformation reduces toxicity of arsenic to soil dwelling microorganism and plant

Ecotoxicology and Environmental Safety, 2019

Rhizospheric and plant root associated microbes generally play a protective role against arsenic ... more Rhizospheric and plant root associated microbes generally play a protective role against arsenic toxicity in rhizosphere. Rhizospheric microbial interaction influences arsenic (As) detoxification/mobilization into crop plants and its level of toxicity and burden. In the present investigation, we have reported a rhizospheric fungi Aspergillus flavus from an As contaminated rice field, which has capability to grow at high As concentration and convert soluble As into As particles. These As particles showed a reduced toxicity to soil dwelling bacteria, fungi, plant and slime mold. It does not disrupt membrane potential, inner/outer membrane integrity and survival of the free N 2 fixating bacteria. In arbuscular mycorrhiza like endophytic fungi Piriformospora indica, these As particles does not influence mycelial growth and plant beneficial parameters such as phosphate solubilizing enzyme rAPase secretion and plant root colonization. Similarly, it does not affect plant growth and chlorophyll content negatively in rice plant. However, these As particles showed a poor absorption and mobilization in plant. These As particle also does not affect attachment process and survival of amoeboid cells in slime mold, Dictyostelium discoideum. This study suggests that the process of conversion of physical and chemical properties of arsenic during transformation, decides the toxicity of arsenic particles in the rhizospheric environment. This phenomenon is of environmental significance, not only in reducing arsenic toxicity but also in the survival of healthy living organism in arsenic-contaminated rhizospheric environment.

Presence of Zearalenone in Cereal Grains and Its Exposure Risk Assessment in Indian Population

Journal of Food Science, 2018

Zearalenone (ZEA) is a toxic metabolite of Fusarium genera that frequently contaminates cereal gr... more Zearalenone (ZEA) is a toxic metabolite of Fusarium genera that frequently contaminates cereal grains. India being a tropical country provides suitable conditions for fungal invasion to the cereals. In the absence of any regulatory limits for ZEA in India, the present study was carried out to analyze the contamination levels of ZEA in different cereal samples consumed by Indian population and its exposure assessment through intake. Out of 117 cereal samples comprising of wheat, rice, corn, and oats, 70 (84%) were found to be positive for ZEA contamination, among which 24 (33%) samples exceeded the permissible limits proposed by European Union when analyzed by high‐performance liquid chromatography. The positive samples were further validated by Liquid Chromatography‐Mass Spectroscopy (LC‐MS) analysis. Based on the quantitative estimation of ZEA contamination in cereals and their daily consumption values, the probable daily intake of ZEA was found to be 16.9‐ and 7.9‐fold higher in r...

A novel function of TLR4 in mediating the immunomodulatory effect of Benzanthrone, an environmental pollutant

Toxicology letters, Jan 5, 2017

Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the sp... more Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated. Further, the potential membrane receptor targets (TLRs) of BA and its interaction with TLRs was investigated using computational methods. Professional phagocytes play pivotal roles in sensing bacteria through pathogen-associated molecular patterns (PAMPs) by various pathogen recognition receptors (PRRs), including Toll-like receptors (TLRs). Several studies have implicated these TLRs in the amplific...

Epidermal benzo[a]pyrene metabolism and DNA-binding in Balb/C mice: Inhibition by ellagic acid

Xenobiotica, 1984

Topical application of ellagic acid, a common plant phenol, to control or to 3-methylcholanthrene... more Topical application of ellagic acid, a common plant phenol, to control or to 3-methylcholanthrene (3-MC) pretreated Balb/C mice, resulted in significant inhibition of hepatic and epidermal microsomal aryl hydrogen hydroxylase activity, and of benzo[a]pyrene (BP) binding to epidermal and hepatic DNA in vivo. In vitro addition of ellagic acid (0.25 mM) to epidermal microsomal incubation systems from either control or 3-MC-treated animals resulted in 62-75% inhibition of BP binding to calf thymus DNA. These studies suggest that ellagic acid could prove useful in understanding and/or modulating polyaromatic hydrocarbon carcinogenesis.

Assessment of the effectiveness of open defecation free system on the incidence of faecal contamination on environment through microbial source tracking

The aim of this study was to assess the effectiveness of open defecation free (ODF) system on the... more The aim of this study was to assess the effectiveness of open defecation free (ODF) system on the incidence of faecal contamination on environment (water, soil and food mediums). The magnitude of contamination of environmental medium of ODF and non-open defecation free (n-ODF) villages by faecal indicator bacteria (FIB) in three states of India, was investigated. The FIB positive samples were further processed to determine the source of faecal contamination using Bacteroidale molecular markers for human (HuBac). The matrix of relative risk (RR) due to FIB and HuBaC contamination was developed to assess the effectiveness of ODF interventions. When compared to ODF villages, the RR of faecal contamination in n-ODF villages was estimated 11.25 times more likely in groundwater, 2.68 times more likely in household storage drinking water, 2.71 times more likely in piped water supplies, 1.13 times more likely in soil and 1.48 times more likely in food. The RR of faecal contamination traceab...

Species differences between rat and human in vitro metabolite profile, in vivo predicted clearance, CYP450 inhibition and CYP450 isoforms that metabolize benzanthrone: Implications in risk assessment

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, Jan 7, 2017

Benzanthrone (BNZ) is a polycyclic aromatic hydrocarbon found in industrial effluent causing skin... more Benzanthrone (BNZ) is a polycyclic aromatic hydrocarbon found in industrial effluent causing skin, respiratory, gastrointestinal, genitourinary, nervous and hemopoietic toxicity. While its toxicity has been well studied, its metabolism in humans has not been investigated. The aim of this study was to characterize species differences in the in vitro metabolism of BNZ in rat and human liver microsomes and to identify the CYP isoforms involved in its metabolism. Upon incubation in liver microsomes, BNZ was found to be a direct substrate of phase I metabolism in both rat and human, undergoing oxidation and reduction. The Km in rat, 11.62 ± 1.49 μM, was two-fold higher than humans (5.97 ± 0.83 μM) suggesting higher affinity for human CYPs. Further, incubation with human rCYPs, BNZ was found to be substrate of multiple CYPs. The predicted in vivo hepatic clearance was 63.55 and 18.91 mL/min/kg in rat and human, respectively, indicating BNZ to be a high clearance compound. BNZ was found to...

Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Clinical and Translational Allergy, 2017

Introduction: Incidence of anaphylaxis is increasing. Data regarding anaphylaxis mortality are li... more Introduction: Incidence of anaphylaxis is increasing. Data regarding anaphylaxis mortality are limited, but conflicting. Our objective was to document anaphylaxis mortality rate (deaths per million population), time trends and specificities according to triggers (iatrogenic, venom, food, unknown), age groups, sex and geographical regions (North and South) in France, between 1979 and 2011. Methods: Data were obtained (1) from database of the National Mortality Center (CEPIDC) to collect cases in which anaphylaxis was included as a cause of death, sex, age, and geographic region of death, (2) from the database of the National Institute for Economical and Statistical studies (INSEE) to define the referent populations. We used a multivariable log-linear Poisson regression model to assess the impact of time period, age, sex and geographic region on anaphylaxis deaths. Results: During the period study, 1603 deaths were collected: 1564 in adults and 39 in children (age <18 year). The overall prevalence of anaphylaxis fatalities was 0.84 per million population (95% IC 0.80-0.88), ranging from 0.08 per million (95% IC 0.05-0.10) in pediatric population to 1.12 per million (95% CI 1.06 to 1.17) in adult population. Annual percentage change for case fatality rate was −2.0% (95% CI −2.5 to −1.5; p < 10 −4) indicating a decrease in case fatality rate during the study period. Anaphylaxis fatality rate was higher in men (1.08 per million [95% IC 1.00 1.16] than women (0.86 per million [95% IC 0.80-0.92]) (p < 10 −4). Triggers of anaphylaxis fatalities were iatrogenic (63%), mostly drugs, venom (14%) and food (0.6%). Unspecified anaphylaxis was frequent (23%). The highest rate was in persons aged >70 years (3.50 per million population per year [95% IC 3.25-3.76]) and the lowest in the pediatric population (p < 10 −4). Only venom-induced mortality rate was higher in South of France (0.16 per million [95% IC 0.13-0.19]) compared with the North (0.11 per million [95% IC 0.09-0.13]) (p = 0.004). Only 8 food-induced fatalities were recorded (age <35 years in 7 cases). Conclusion: Overall anaphylaxis mortality rate is decreasing over the three last decades in France. We confirm that iatrogenic causes are the most frequent causes. Older age and male sex are risk factors of fatal anaphylaxis of any cause except for food-induced anaphylaxis.

Hepatomyoencephalopathy in Malkangiri district of Odisha, India

Current Science, 2017

During September through November 2016, some 100 children died due to acute brain disease in Malk... more During September through November 2016, some 100 children died due to acute brain disease in Malkangiri district, southern Odisha, India. Most deaths were at first attributed to Japanese encephalitis (JE) due to the following reasons: JE had been reported in Malkangiri district in previous years and diagnostic test for JE was positive in a few children in 2016; JE season is September through November; the vector mosquitoes and amplifying hosts, namely pigs, are prevalent in Malkangiri district. However, a number of cases turned out negative for JE test. Therefore, in the last week of October, the Department of Health, Government of Odisha, constituted a team to investigate the cases of non-JE acute brain disease with high mortality. We conducted a rapid review and investigations during the first two weeks of November. Two of us (G.A. and M.M.P.) had visited Malkangiri district during October when the clinical pattern of non-JE cases was found to be stereotyped: relatively abrupt ons...

Argemone oil, an edible oil adulterant, induces systemic immunosuppression in balb/c mice in an oral 28 days repeated dose toxicity study

Chemico-biological interactions, Jan 12, 2018

Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition call... more Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2). At the functional level, AO exposure significantly abrogated the mixed lymphocyte reaction and mitogen-stimulated lymphoproliferative activity of T and B cells, which is reflective of profound lymphocyte dysfunction upon antigen exposure. In concordance with the los...

CSIR-Indian Institute of Toxicology Research, Lucknow

Current Science, 2015

CSIR-Indian Institute of Toxicology Research (IITR), Lucknow, established on 4 November 1965, is ... more CSIR-Indian Institute of Toxicology Research (IITR), Lucknow, established on 4 November 1965, is one of the pioneer institutions dealing with toxicology research in the Asia-Pacific region. IITR is the only laboratory in the CSIR family to be awarded the Good Laboratory Practice certification. The five decades of expertise and knowledge base in toxicology research have empowered the Institute to conduct studies in the following niche areas: (i) Food, drug and chemical toxicology, (ii) nanotherapeutics and nanomaterial toxicology, (iii) systems toxicology and health risk assessment, (iv) environmental toxicology, and (v) regulatory toxicology. The highlights of some of the scientific achievements for the year 2014 are described in this article.

Fatty Acid Composition Including<i>Trans</i>-Fatty Acids in Edible Oils and Fats: Probable Intake in Indian Population

Journal of Food Science, Sep 5, 2012

: The susceptibility of trans‐fat to the human health risk prompted the Food and Agriculture Org... more : The susceptibility of trans‐fat to the human health risk prompted the Food and Agriculture Organization (FAO) and World Health Organization (WHO) to prepare regulations or compulsory claims for trans‐fatty acids (TFA) in edible oils and fats. In this study, analysis of fatty acid composition and TFA content in edible oils and fats along with the possible intake of trans‐fat in Indian population was carried out. The analysis was carried out as per the Assn. of Official Analytical Chemists (AOAC) methodology and the results were statistically analyzed. The average TFA content in nonrefined mustard and refined soybean oils exceeded by 1.16‐ to 1.64‐fold as compared to the Denmark limit of 2% TFA in fats and oils destined for human consumption. In branded/nonbranded butter and butter oil samples, average TFA limit exceeded by 4.2‐ to 9.5‐fold whereas hydrogenated vegetable oil (HVO) samples exceeded the limit by 9.8‐fold, when compared to Denmark standards. The probable TFA intake per day through different oils in Indian population were found to be less than WHO recommendation. However Punjab having highest consumption of HVO (–15 g/d) showed 1.09‐fold higher TFA intake than the WHO recommendation, which is alarming and may be one of the factors for high cardiovascular disease mortality rate that needs further elucidation. Thus there is a need to prescribe TFA limit for edible oil, butter, and butter oil in India and to reduce the already proposed TFA levels in HVO to safeguard the health of consumers.Practical Application: The probable daily intake of trans‐fatty acid (TFA) especially through hydrogenated vegetable oil (HVO) was assessed. In absence of any specification for TFA and fatty acid composition for edible oils, butter, and butter samples, a pressing need was felt to prescribe TFA limit in India. The study indicates that TFA intake through HVO consumption is higher in States like Punjab than the recommended daily intake prescribed by WHO. Hence, strategies should be adopted to either decrease the consumption of HVO or to modify the industrial processing method of HVO with less content of TFA to safeguard the health of consumers.

Detection of polycyclic aromatic hydrocarbons in commonly consumed edible oils and their likely intake in the Indian population

Journal of the American Oil Chemists' Society, Dec 1, 2004

Edible oils such as coconut, groundnut, hydrogenated vegetable, linseed, mustard, olive, palm, re... more Edible oils such as coconut, groundnut, hydrogenated vegetable, linseed, mustard, olive, palm, refined vegetable, rice bran, safflower, sesame, soybean, and sunflower were analyzed for the presence of light and heavy polycyclic aromatic hydrocarbon (PAH) residues using liquid-liquid extraction, cleanup on a silica gel column, and resolution and determination by HPLC using a fluorescence detector. Ten PAH viz. acenaphthene, anthracene, benzo(a)pyrene, benzo(e)pyrene, benz(ghi)perylene, chrysene, coronene, cyclopenta(def)phenanthrene, phenanthrene, and pyrene were monitored. Analysis of 296 oil samples showed that 88.5% (262) samples were contaminated with different PAH. Of 262 contaminated edible oil samples, 66.4% of the samples showed PAH content of more than the 25 µg/kg recommended by the German Society for Fat Science. The total PAH content was highest in virgin olive oil (624 µg/kg) and lowest in refined vegetable oils (40.2 µg/kg). The maximum content (265 µg/kg) of heavy PAH was found in olive oil and the minimum (4.6 µg/kg) in rice bran oil. Phenanthrene was present in 58.3% of the oil samples analyzed, followed by anthracene (53%). Among the heavy PAH, benzo(e)pyrene was observed in 31.2% of the samples followed by benzo(a)pyrene (25.5%). The intake of PAH was highest through olive oil (20.8 µg/day) followed by soybean oil (5.0 µg/day) and lowest through refined vegetable oil (1.3 µg/day). Based on these monitoring studies, international and national guidelines for permissible levels of PAH can be prepared so as to restrict the intake of these toxic contaminants.

A Simple Method for Simultaneous Determination of Basic Dyes Encountered in Food Preparations by Reversed-Phase HPLC

Journal of AOAC International, Nov 1, 2011

The present method utilizes a simple pretreatment step, cleanup on polyamide SPE cartridges, and ... more The present method utilizes a simple pretreatment step, cleanup on polyamide SPE cartridges, and HPLC resolution on reversedphase C18 for the detection of the three basic nonpermitted dyes encountered in food matrixes. Polyamide cartridges were chosen because both acidic and basic dyes can be cleaned up due to their amphoteric nature. Analysis was performed on a reversed-phase C18 µ-Bondapak column using the isocratic mixture of acetonitrile-sodium acetate with a flow rate of 1.5 mL/min and a programmable λ max specific visible detection to monitor colors, achieving higher sensitivity and expanded scope to test multicolor blends. All the colors showed linearity with the regression coefficient, from 0.9983 to 0.9995. The LOD and LOQ ranged between 0.107 and 0.754 mg/L and 0.371 and 2.27 mg/L or mg/kg, respectively. The intraday and interday precision gave good RSDs, and percentage recoveries in different food matrixes ranged from 75 to 96.5%. The study demonstrates that the use of a combination of a simple SPE cleanup and HPLC resolution with UV-Vis end point detection was successful in screening the presence of these three basic nonpermitted dyes individually or in blend, in a variety of food matrixes.

Correction: Topical Application of Ochratoxin A Causes DNA Damage and Tumor Initiation in Mouse Skin

PLOS ONE, Nov 26, 2018

Incorrect images were used for the Control and OTA (80μg) panels of Fig 1D of this article [1], w... more Incorrect images were used for the Control and OTA (80μg) panels of Fig 1D of this article [1], which are duplicates of the Control and CTN (48h) panels, respectively, in Fig 2B of the following article previously published in the journal Toxicological Sciences: Citrinin-Generated Reactive Oxygen Species Cause Cell Cycle Arrest Leading to Apoptosis via the Intrinsic Mitochondrial Pathway in Mouse Skin [2]

Simultaneous Determination of Acetaminophen and Synthetic Color(s) by Derivative Spectroscopy in Syrup Formulations and Validation by HPLC: Exposure Risk of Colors to Children

Aaps Pharmscitech, Nov 6, 2014

Color additives are used in pediatric syrup formulations as an excipient; though not prerequisite... more Color additives are used in pediatric syrup formulations as an excipient; though not prerequisite, but pediatric syrup formulations are normally colored. An attempt has been made to measure simultaneously the single drug, acetaminophen (AT), along with the colors, carmoisine (CA), erythrosine (ET), and sunset yellow FCF (SSY) added in it by three derivative spectroscopy methods namely, 1st order, ratio, and differential derivative methods. Moreover, evaluation has been made for the exposure assessment of the colors added as excipient because some colors have been reported to cause allergic reactions and hypersensitivity in children. The present methods provide simple, accurate, and reproducible quantitative determination of the drug, AT, along with the color in synthetic mixtures and commercial drug formulations without any interference. The limit of detection varied from 0.0001-0.31 μg/ml while limit of quantification ranged from 0.002-1.04 μg/ml in all the three methods. The calibration curve of all the three derivative methods exhibited good linear relationship with excellent regression coefficients (0.9986-1.000). Both intra-day and inter-day precisions showed %RSD value less than 2% while the percentage recovery was found between 96.8-103.8%. The sensitivity of the proposed methods is almost comparable to HPLC and thus, can be used for determination of drug AT, and color simultaneously in pharmaceutical formulation on routine basis. The present methods also showed that colors like SSY and ET are saturating more than 50% of acceptable daily intake (ADI) value which is alarming and needs to be considered for modification by regulatory authorities to safeguard the health of children.

Intake pattern of synthetic colours by different age and socio-economic consumer groups of Lucknow, India

International Journal of Food, Nutrition and Public Health, 2010

Exposure assessment of synthetic food colours in different age and socioeconomic groups of consum... more Exposure assessment of synthetic food colours in different age and socioeconomic groups of consumers revealed that on average intake of food commodities, only Erythrosine exceeded the acceptable daily intake (ADI) limit in the 1–10 and 11–20 years age groups through sugar toys on both normal (19–115%) and festive occasions (8–236%). However, on maximum likely intake of foods, Sunset Yellow FCF, Tartrazine, Carmoisine and Erythrosine were found to exceed the ADI limits several times, ranging between 14–1, 138% in 1–10 year and 45–765% in 11–20 year age subjects. Among foods predominantly consumed by children, crushed ice, ice-candy, ice cream, beverages, sweets and sugar toys were identified as the culprits leading to excessive intake of colours. The permitted levels of colours allowed in food commodities, need to be reviewed periodically and should be governed by technological necessity and the consumption profiles of the food commodity so that colours do not cross the prescribed ADI-based safety umbrella and pose a threat to vulnerable populations.

Toxicity of Naturally Occurring Anthraquinones

Advances in Molecular Toxicology, 2017

Abstract Among the vast array of secondary metabolites produced by plants, anthraquinones (AQs) a... more Abstract Among the vast array of secondary metabolites produced by plants, anthraquinones (AQs) are the group of compounds produced by different plants of various families such as Polygonaceae, Rhamnaceae, Rubiaceae, Fabaceae, Xanthorrhoeaceae, Leguminosae, and Liliacae. Owing to their biological and chemical diversity, AQs have wide industrial applications in food, pharmaceutical, and paper industries. Despite their diverse application, anthraquinones have been reported to be toxic to experimental animals. However, very little is known about their toxicity on the human population. In this chapter, the metabolic routes for the biosynthesis of AQs in plants have been described. Efforts have been focused on the profile of AQs present in different plant species and their toxic effects on the various animal models and in humans.

Sustained Release Tablets of Sorafenib-Silibinin Combinations for the Treatment of Hepatocellular Carcinoma

International Journal of Applied Pharmaceutics, 2018

Objective: The aim of this study was to develop polymer coated sustained release tablet using sor... more Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma.Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation.Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommenda...

Corrigendum to “A novel function of TLR4 in mediating the immunomodulatory effect of Benzanthrone, an environmental pollutant” [Toxicol. Lett. 276 (May) (2017) 69–84]

Toxicology Letters, 2019

Simple Extraction Cum RP-HPLC Method for Estimation of Nanotized Quercetin in Serum and Tissues of Mice

Pharmaceutical Chemistry Journal, 2018

In recent years, several studies have focused on antioxidant, anti-inflammatory, and anti-cancer ... more In recent years, several studies have focused on antioxidant, anti-inflammatory, and anti-cancer activities of quercetin (3,3¢,4¢,5,-pentahydroxyflavone). The nanotization of quercetin was shown to enhance its therapeutic efficacy due to smaller particle size. In the present study, an additional step was added to simple extraction cum RP-HPLC method for the quantification of nanotized quercetin (nQ) in biological samples to understand the pharmacokinetics and biodistribution of nQ following intravenous administration. The proposed method involves extraction of nQ from blood serum and tissues of mice with 2N HCl in comparison to well-known DMSO:MeOH mix method. The HCl extraction was found to be 2-3 times more efficient than DMSO:MeOH mix method. Results showed that the amount of nQ at various time intervals in the serum and tissues was 2-3 fold greater for HCl extraction than for DMSO:MeOH mix method, suggesting that HCl extraction must take into account nQ bound with protein. The reversed-phase HPLC was used for nQ detection, which showed the nQ retention time of 3.2 min. The limit of detection of nQ in blood serum was found to be 0.1 mg/mL. The proposed method was also validated in terms of linearity, precision, and accuracy.

Fungal mediated biotransformation reduces toxicity of arsenic to soil dwelling microorganism and plant

Ecotoxicology and Environmental Safety, 2019

Rhizospheric and plant root associated microbes generally play a protective role against arsenic ... more Rhizospheric and plant root associated microbes generally play a protective role against arsenic toxicity in rhizosphere. Rhizospheric microbial interaction influences arsenic (As) detoxification/mobilization into crop plants and its level of toxicity and burden. In the present investigation, we have reported a rhizospheric fungi Aspergillus flavus from an As contaminated rice field, which has capability to grow at high As concentration and convert soluble As into As particles. These As particles showed a reduced toxicity to soil dwelling bacteria, fungi, plant and slime mold. It does not disrupt membrane potential, inner/outer membrane integrity and survival of the free N 2 fixating bacteria. In arbuscular mycorrhiza like endophytic fungi Piriformospora indica, these As particles does not influence mycelial growth and plant beneficial parameters such as phosphate solubilizing enzyme rAPase secretion and plant root colonization. Similarly, it does not affect plant growth and chlorophyll content negatively in rice plant. However, these As particles showed a poor absorption and mobilization in plant. These As particle also does not affect attachment process and survival of amoeboid cells in slime mold, Dictyostelium discoideum. This study suggests that the process of conversion of physical and chemical properties of arsenic during transformation, decides the toxicity of arsenic particles in the rhizospheric environment. This phenomenon is of environmental significance, not only in reducing arsenic toxicity but also in the survival of healthy living organism in arsenic-contaminated rhizospheric environment.

Presence of Zearalenone in Cereal Grains and Its Exposure Risk Assessment in Indian Population

Journal of Food Science, 2018

Zearalenone (ZEA) is a toxic metabolite of Fusarium genera that frequently contaminates cereal gr... more Zearalenone (ZEA) is a toxic metabolite of Fusarium genera that frequently contaminates cereal grains. India being a tropical country provides suitable conditions for fungal invasion to the cereals. In the absence of any regulatory limits for ZEA in India, the present study was carried out to analyze the contamination levels of ZEA in different cereal samples consumed by Indian population and its exposure assessment through intake. Out of 117 cereal samples comprising of wheat, rice, corn, and oats, 70 (84%) were found to be positive for ZEA contamination, among which 24 (33%) samples exceeded the permissible limits proposed by European Union when analyzed by high‐performance liquid chromatography. The positive samples were further validated by Liquid Chromatography‐Mass Spectroscopy (LC‐MS) analysis. Based on the quantitative estimation of ZEA contamination in cereals and their daily consumption values, the probable daily intake of ZEA was found to be 16.9‐ and 7.9‐fold higher in r...

A novel function of TLR4 in mediating the immunomodulatory effect of Benzanthrone, an environmental pollutant

Toxicology letters, Jan 5, 2017

Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the sp... more Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated. Further, the potential membrane receptor targets (TLRs) of BA and its interaction with TLRs was investigated using computational methods. Professional phagocytes play pivotal roles in sensing bacteria through pathogen-associated molecular patterns (PAMPs) by various pathogen recognition receptors (PRRs), including Toll-like receptors (TLRs). Several studies have implicated these TLRs in the amplific...

Epidermal benzo[a]pyrene metabolism and DNA-binding in Balb/C mice: Inhibition by ellagic acid

Xenobiotica, 1984

Topical application of ellagic acid, a common plant phenol, to control or to 3-methylcholanthrene... more Topical application of ellagic acid, a common plant phenol, to control or to 3-methylcholanthrene (3-MC) pretreated Balb/C mice, resulted in significant inhibition of hepatic and epidermal microsomal aryl hydrogen hydroxylase activity, and of benzo[a]pyrene (BP) binding to epidermal and hepatic DNA in vivo. In vitro addition of ellagic acid (0.25 mM) to epidermal microsomal incubation systems from either control or 3-MC-treated animals resulted in 62-75% inhibition of BP binding to calf thymus DNA. These studies suggest that ellagic acid could prove useful in understanding and/or modulating polyaromatic hydrocarbon carcinogenesis.

Studies on the interaction of anthraquinones with bovine serum albumin (BSA) by Molecular docking approaches

by Neeraj Verma and Mukul Das

Studies on the interaction of anthraquinones with bovine serum albumin (BSA) by Moleculasr docking approaches.

Integrated approaches to find the therapeutic molecular targets of Sunset Yellow implicated as anti-inflammatory agent.

by Neeraj Verma and Mukul Das