Papers by Prabhakara Yallapragada
International Journal of Bioassays
Cadmium is a well known heavy metal toxicant which can interfere with metabolism of carbohydrates... more Cadmium is a well known heavy metal toxicant which can interfere with metabolism of carbohydrates, proteins and lipids by inhibiting the enzymes involved in the processes. In the present investigation, the effect of cadmium was evaluated on these biochemical constituents in two fresh water fish fry Labeo rohita and Cyprinus carpio. Fish fry of Labeo rohita and Cyprinus carpio were exposed to their respective sub-lethal concentrations (1/5th of LC50), 0.1998 ppm and 4.938 ppm of cadmium for a period of 20days. Total carbohydrates, proteins and lipids were estimated by standard biochemical procedures in control and exposed fish fry. Results showed significant fall in all the biochemical constituents and energy levels of exposed fish fry, indicating that the organism is under toxicant stress.
Cadmium is a well known heavy metal toxicant which can interfere with metabolism of carbohydrates... more Cadmium is a well known heavy metal toxicant which can interfere with metabolism of carbohydrates, proteins and lipids by inhibiting the enzymes involved in the processes. In the present investigation, the effect of cadmium was evaluated on these biochemical constituents in two fresh water fish fry Labeo rohita and Cyprinus carpio. Fish fry of Labeo rohita and Cyprinus carpio were exposed to their respective sub-lethal concentrations (1/5th of LC50), 0.1998 ppm and 4.938 ppm of cadmium for a period of 20days. Total carbohydrates, proteins and lipids were estimated by standard biochemical procedures in control and exposed fish fry. Results showed significant fall in all the biochemical constituents and energy levels of exposed fish fry, indicating that the organism is under toxicant stress.

ARTICLE INFO ABSTRACT Kolleru lake, the largest freshwater lake in India was studied for the asse... more ARTICLE INFO ABSTRACT Kolleru lake, the largest freshwater lake in India was studied for the assessment of dissolved organic matter distribution and the influence on the lake hydro chemical characteristics. The study revealed the significant influence of freshwater inputs and their control in the distribution of dissolved organic matter (DOM) throughout the lake. Correlation analysis indicated that the DOM mineralization decreased the DO concentration during the monsoon and post-monsoon, making the lake under saturated (upto 7% DO saturation) whereas, during pre-monsoon DO in the lake was not controlled by DOM. Mixing plots of DOC, DON and DOP versus salinity suggested that DON and DOP acted as sink during all the seasons, whereas DOC acted as a source due to domination of production over mineralization. This is the baseline information regarding the dissolved organic matter and will be useful for further intensive study on biogeochemistry of the lake.
Chemistry and Ecology, 2015

Ecotoxicology, 2014
The objective of the present study is to evaluate a sensitive indicator of cadmium by measuring o... more The objective of the present study is to evaluate a sensitive indicator of cadmium by measuring oxygen consumption and carotenoid concentration in post larvae of Penaeus monodon. The post larvae of P. monodon were exposed to 0.12 and 0.24 mg/L of cadmium in the laboratory for a period of 30 days. These concentrations represent 1/10th and 1/5th of 96 h LC50 value for the post larvae. Oxygen consumption and carotenoid concentration were measured at 24, 48, 96 h, 10 and 30 days of cadmium exposure. The results indicated an inhibition of routine oxygen consumption in post larvae at different intervals of exposure from 24 h to 30 days but the effect was statistically significant (P < 05) at 30 days of exposure at both sub lethal concentrations, where the inhibition was 38.5 % at 0.24 mg/L and 21.6 % at 0.12 mg/L. On the other hand, carotenoid concentrations increased gradually with increasing period of exposure as well as concentration, and this increase was statistically significant (P < 0.05) from 96 h onwards on exposure to 0.12 mg/L and from 48 h onwards on exposure to 0.24 mg/L of cadmium, with an overall highest increase of 135 %. As carotenoid content is an indicator of tissue oxygen, inhibition of routine oxygen consumption might have resulted in enhancing the levels of carotenoid. From the present data, it is evident that carotenoid concentration can be considered as a sensitive indicator of cadmium toxicity than routine oxygen consumption in the post larvae of P. monodon. The present investigation is also relevant for environmental monitoring of cadmium in coastal waters before it is used for aquaculture.

Pharmacology Amp Toxicology, Sep 1, 1990
Previous studies from our laboratory have indicated that chlordecone (Keponee, CD), an organochlo... more Previous studies from our laboratory have indicated that chlordecone (Keponee, CD), an organochlorine insecticide, inhibited cardiac sodium pump activity and catecholamine uptake suggesting that CD may interfere with cardiac function. Sarcoplasmic reticulum (SR) calcium pump has an important role in myocardial contraction and relaxation, besides Naf transport. Since CD interferes with cardiac Na+ ion translocases, we have studied CD effects on cardiac SR calcium pump activity. Experiments were carried out both in vitro and in vivo. SR was isolated from heart ventricles of male Sprague-Dawley rats. Cardiac SR Ca'+-ATPase, 45Ca-uptake and cAMP as well as calmodulin (CaM) dependent protein phosphorylation were measured. Ca'+-ATPase was differentiated into low affinity and high affinity forms by measuring the activity using 50 and 0.7 pM free Ca'+ respectively. CD in vitro inhibited 45Ca-uptake by SR in a concentration dependent manner with an IC50 value of 7 pM and SR 45Ca-uptake was totally inhibited at 20-30 pM CD. In agreement with this, both high affinity and low affinity Ca'+-ATPases, which are involved in Ca2+ transport across membranes, were also inhibited by CD in a concentration dependent manner with IC50 values of 0.7 and 3.2 pM respectively. Both Ca*+-ATPase and 45Ca-uptake by cardiac SR were significantly lower in rats treated with CD (25, 50 or 75 mg/kg) when compared to control rats. cAMP as well as CaM significantly elevated the "P-binding to SR proteins in vitro to about 70-80%. In the presence of CD, this "P-binding was reduced, however, not concentration dependent. In agreement with in vitro studies, I2P-bound to proteins was significantly lowered in rats treated with CD. SDSpolyacrylamide gel electrophoresis of the cardiac SR revealed the presence of at least 30 comassie blue-stainable bands with mobilities corresponding to molecular weights ranging from 9 to 120 kDa using 15% acrylamide gels. Autoradiographs from samples incubated in the presence of cAMP or CaM indicated 3'P-incorporation in 7 bands. Of these, bands corresponding to about 24 kDa and adjacent lower molecular weights decreased in their intensity by CD in vitro as well as in vivo. These results indicate that CD treatment may be reducing SR calcium transport mechanisms by altering phosphorylation of a number of proteins including phospholamban in rat cardiac SR.

Journal of Toxicology and Environmental Health, Nov 1, 1991
We have recently reported that the triorganotins are effective inhibitors of calmodulin (CaM) act... more We have recently reported that the triorganotins are effective inhibitors of calmodulin (CaM) activity in vitro. The present experiments were designed to investigate the in vivo effects of triorganotins, that is, tributyltin (TBT), triethyltin (TET), and trimethyltin (TMT) on rat brain CaM activity. Male Sprague‐Dawley rats were treated orally with TET (0.5, 1.0, and 1.5 mg/kg/d), TMT (0.75, 1.50, and 2.50 mg/kg/d), and TBT (0.75, 1.50, and 2.50 mg/kg/d) for 6 d and they were sacrificed 24 h after the last dose. There was significant loss of body weight in the high‐dose group of the organotin treated rats. Ca‐ATPase activity was determined in rat brain synaptic membranes. TET and TMT inhibited Ca‐ATPase in a dose‐dependent manner but TBT exhibited its inhibitory effect only at the highest dose (2.5 mg/kg/d). The inhibition of Ca‐ATPase by these triorganotin compounds was reversed to control levels by the addition of CaM (5–10 μg) exogenously. The CaM levels of the synaptic membranes of the organotin‐treated rats were not significantly changed. The data presented in this paper demonstrate that triorganotins impair the Ca‐pump activity by interacting with CaM, which is a regulatory protein of Ca‐ATPase. The present in vivo data and our previously reported in vitro data together indicate that triorganotins associated neurotoxicity may be due to an altered CaM activity in brain.

Journal of Toxicology and Environmental Health, 1990
In vitro effects of three triorganotins--tributyltin (TBT), triethyltin (TET), and trimethyltin (... more In vitro effects of three triorganotins--tributyltin (TBT), triethyltin (TET), and trimethyltin (TMT)--on calmodulin (CaM) activity were studied. Stimulation of Ca2(+)-ATPase of rat brain synaptic membranes and phosphodiesterase (PDE) of bovine brain were assayed as indicators of CaM activity. The rat synaptic membranes were prepared and CaM was depleted by washing with 1 mM EGTA. All the three organotins inhibited the basal as well as CaM-stimulated Ca2(+)-ATPase in a concentration-dependent manner, suggesting their interaction with calcium pump. However, CaM-stimulated Ca2(+)-ATPase was more sensitive than the basal enzyme. The order of potency of the three organotin compounds was TBT greater than TET greater than TMT. The IC50 values of Ca2(+)-ATPase (basal) were 0.63, 35, and approximately 800 microM, respectively, whereas the values for CaM-stimulated Ca2(+)-ATPase were 0.05, 0.8, and 18 microM for TBT, TET, and TMT, respectively. CaM-deficient PDE did not show any sensitivity to these three organotin compounds, while TBT and TET significantly decreased the CaM-stimulated PDE activity. TMT, which was the least effective inhibitor of Ca2+ pump, did not alter PDE activity. Further, the inhibition of CaM-stimulated Ca2(+)-ATPase activity by these organotins could be reversed by excess addition of CaM. These results suggest that the organotins interact with CaM activity, as evidenced by their potent effect on CaM-dependent Ca2(+)-ATPase and PDE activities.

Archiv Fur Experimentelle Pathologie Und Pharmakologie, Mar 1, 1992
Long term amiodarone (AM) therapy has been associated with several side effects including neuroto... more Long term amiodarone (AM) therapy has been associated with several side effects including neurotoxicity. Since AM alters Ca2+ regulated events, we have studied its effects on the compartmentation of free Ca2+ in the synaptosomes as an attempt to understand the mechanism of AM and its metabolite, desethylamiodarone (DEA)-induced neurotoxicity. Intact brain synaptosomes were prepared from male Sprague-Dawley rats. Both AM and DEA produced a concentration dependent increase in intrasynaptosomal free Ca2+ concentration ([Ca2]i) to micromolar levels. The increase in [Ca2]i was not transient and a steady rise was observed with time. Omission of Ca2+ from the external medium prevented the AM- and DEA-induced rise in [Ca2+]i suggesting that AM and DEA increased the intracellular [Ca2+]i due to increased influx of Ca2+ from external medium. AM- and DEA-induced increase in intrasynaptosomal [Ca2+]i was neither inhibited by a calcium channel blocker, verapamil, nor with a Na+ channel blocker, tetrodotoxin. However, the blockade of [Ca2+]i rise by AM and DEA was observed with MK-801, a receptor antagonist indicating that AM and DEA induced rise in [Ca2+]i is through receptor mediated channel. Both AM and DEA also inhibited N-methyl-D-aspartic acid (NMDA)-receptor binding in synaptic membranes in a concentration dependent manner, DEA being more effective, indicating that AM and DEA compete for the same site as that of NMDA and confirm the observation that these drugs increase intrasynaptosomal [Ca2+]i through receptor mediated channel. 45Ca accumulation into brain microsomes and mitochondria was significantly inhibited by AM and DEA, but without any effect on the Ca2+ release from these intracellular organelles.(ABSTRACT TRUNCATED AT 250 WORDS)

Ecotoxicol Environ Safety, 1996
Earlier investigations from this laboratory suggest that lead interferes with the calcium homeost... more Earlier investigations from this laboratory suggest that lead interferes with the calcium homeostasis of rat brain through modulation of an inositol polyphosphate second-messenger system. The present investigation was initiated to study the comparative effects of lead chloride and lead acetate on synaptosomal and microsomal Ca2+-ATPase of rat cerebral cortex and cerebellumin vitro.The synaptic plasma membranes and microsomes were prepared by using sucrose gradient (1.2–0.8M). The assay of Ca2+-ATPase was done by hydrolysis of ATP and the liberated inorganic phosphate was estimated. Both lead chloride and lead acetate at micromolar concentrations significantly inhibited the Ca2+-ATPase of synaptic plasma membranes and microsomes of cerebral cortex and cerebellum in a concentration-dependent manner. The IC50values of Ca2+-ATPase for both lead salts in synaptosomes were significantly lower (P< 0.05) than that of microsomes, indicating more sensitivity. Significantly (P< 0.05) lower IC50values for both synaptosomal and microsomal Ca2+-ATPase were obtained for lead acetate than for lead chloride. The results suggest that lead acetate is more potent than lead chloride in inhibiting the Ca2+-ATPase. The microsomal Ca2+uptake was also studied in cerebellum and cerebral cortex in the presence of different concentrations of both the lead salts. However, these lead saltsin vitrodid not reveal a significant (P< 0.05) change in the microsomal Ca2+uptake of cerebellum and cerebral cortex. But earlier investigations indicated thatin vitrolead (0.25–2 μM) inhibits inositol 1,4,5-triphosphate-mediated Ca2+uptake and release in microsomes of rat cerebellum.

J Appl Toxicol, 1996
The present investigation was initiated to study the differential effects of mercury salts on cal... more The present investigation was initiated to study the differential effects of mercury salts on calcium pump activity of rat cerebellum and cerebral cortex in vitro. The calcium pump activity was studied by assaying calcium-adenosine triphosphatase (Ca(2+)-ATPase) in synaptic plasma membranes (SPMs) and microsomes of cerebellum and cerebral cortex in the presence of different micromolar concentrations of mercury and methylmercury. The 45Ca uptake in microsomes of cerebellum and cerebral cortex was also determined in the presence of both the salts of mercury. The SPMs and microsomes were prepared by differential centrifugation using a sucrose gradient (0.8/1.2 M). The Ca(2+)-ATPase activity was determined by estimating the inorganic phosphate. The 45Ca uptake was measured in microsomes by using 45CaCl2. Calcium-ATPase in SPMs was significantly inhibited by these two mercury salts in a concentration-dependent manner. In cerebellum and cortex, the IC50 values for mercuric chloride were 0.065 and 0.081 microM, respectively, whereas they were 0.354 and 0.384 microM for methylmercury chloride, indicating that mercuric chloride was more potent in inhibiting the plasma membrane Ca2+ extrusion process when compared to methylmercury chloride. As seen in SPMs, Ca(2+)-ATPase and 45Ca uptake in microsomes were also significantly inhibited in both cerebellum and cortex by mercury salts in a concentration-dependent manner, the effect being greater with mercuric chloride. These results indicate that both mercury and methylmercury inhibited the Ca2+ pumps located in SPMs and microsomes differentially, and to some extent the effects were also region specific.
Http Dx Doi Org 10 1080 02757541003785809, May 13, 2010
... Chinni and Yallapragada 1919. Chinni, S. and Yallapragada, PR 2000. ... The reported LC 50 va... more ... Chinni and Yallapragada 1919. Chinni, S. and Yallapragada, PR 2000. ... The reported LC 50 values for 96 h on P. indicus PL are 7.223 mg·L −1 (20) for lead, 6.2231 mg·L −1 (20) for zinc, 3.1191 mg·L −1 (20) for cadmium 1919. Chinni, S. and Yallapragada, PR 2000. ...
Regional Studies in Marine Science, 2015
Asian Journal of Microbiology, Biotechnology and Environmental Sciences

Journal of Environmental Pathology, Toxicology and Oncology, 2015
Ginkgo biloba extract (GbE) is a well known natural antioxidant. In the present investigation, it... more Ginkgo biloba extract (GbE) is a well known natural antioxidant. In the present investigation, its ameliorative effects were tested against lead-induced oxidative stress in rat brain. Four groups of male Wistar rats (100 to 120 g) were used, consisting of eight rats per group. Rats in the control group received 500 ppm of sodium acetate through drinking water, and rats in the other three groups received 500 ppm of lead acetate through drinking water for 4 weeks. Rats in the third and fourth groups were administered (oral) 50 and 100 mg/kg of GbE, respectively, along with lead acetate. The rats were sacrificed after treatment and brains were isolated. Each brain was dissected on ice, and different regions, namely the cerebellum, hippocampus, frontal cortex, and brainstem, were separated. The results revealed a significant (P &amp;amp;lt; .001) increase in reactive oxygen species, catalase, superoxide dismutase, lipid peroxidation products, and total protein carbonyl content, relative to their controls, in all four regions of the brain exposed to lead. These results indicate oxidative stress. Partial restoration was observed for all the parameters just mentioned in different brain regions on treatment with 50 mg/kg GbE. This amelioration was higher with 100 mg/kg GbE, showing dose-dependency. Overall the data suggest that GbE protects against lead-induced oxidative stress in specific regions of rat brain.

Toxicology Letters, 2009
In our earlier investigations, we have demonstrated the alteration of antioxidant enzymes in adul... more In our earlier investigations, we have demonstrated the alteration of antioxidant enzymes in adult rat brain exposed to lead. This study was carried out to investigate the effect of lead on inducing apoptosis by choosing poly (ADP-ribose) polymerase (PARP), bcl-2 and caspase-3 expression as marker proteins in the cerebellum, the hippocampus, the brain stem and the frontal cortex. Adult male rats were treated with lead acetate (500ppm) through drinking water for a period of 8 weeks and parallel controls were maintained on sodium acetate. Both control and exposed rats were sacrificed at intervals of 4 and 8 weeks, brains were isolated and different regions namely the cerebellum, the hippocampus, the frontal cortex and the brain stem were separated and processed to investigate PARP, bcl-2 and caspase-3 expression using western blotting. The results suggest that lead induces region-specific response of expression in apoptotic proteins of rat brain showing more effect in hippocampus and cerebellum and less effect in frontal cortex and brain stem and it is tissue specific. However, results appear to conclude that PARP induced expression in hippocampus and cerebellum was more followed by mitochondrial and cytosolic damage.

Journal of Toxicology and Environmental Health, 1991
We have recently reported that the triorganotins are effective inhibitors of calmodulin (CaM) act... more We have recently reported that the triorganotins are effective inhibitors of calmodulin (CaM) activity in vitro. The present experiments were designed to investigate the in vivo effects of triorganotins, that is, tributyltin (TBT), triethyltin (TET), and trimethyltin (TMT) on rat brain CaM activity. Male Sprague‐Dawley rats were treated orally with TET (0.5, 1.0, and 1.5 mg/kg/d), TMT (0.75, 1.50, and 2.50 mg/kg/d), and TBT (0.75, 1.50, and 2.50 mg/kg/d) for 6 d and they were sacrificed 24 h after the last dose. There was significant loss of body weight in the high‐dose group of the organotin treated rats. Ca‐ATPase activity was determined in rat brain synaptic membranes. TET and TMT inhibited Ca‐ATPase in a dose‐dependent manner but TBT exhibited its inhibitory effect only at the highest dose (2.5 mg/kg/d). The inhibition of Ca‐ATPase by these triorganotin compounds was reversed to control levels by the addition of CaM (5–10 μg) exogenously. The CaM levels of the synaptic membranes of the organotin‐treated rats were not significantly changed. The data presented in this paper demonstrate that triorganotins impair the Ca‐pump activity by interacting with CaM, which is a regulatory protein of Ca‐ATPase. The present in vivo data and our previously reported in vitro data together indicate that triorganotins associated neurotoxicity may be due to an altered CaM activity in brain.

Journal of Environmental Pathology, Toxicology and Oncology, 2014
Moringa oleifera is a tree belonging to Moringaceae family and its leaves and seeds are reported ... more Moringa oleifera is a tree belonging to Moringaceae family and its leaves and seeds are reported to have ameliorative effects against metal toxicity. In the present investigation, M. oleifera seed powder was tested against lead-induced oxidative stress and compared against meso-2, 3-dimercaptosuccinic acid (DMSA) treatment. Male Wistar rats (100-120 g) were divided into four groups: control (2000 ppm of sodium acetate for 2 weeks), exposed (2000 ppm of lead acetate for 2 weeks), Moringa treated (500 mg/kg for 7 days after lead exposure), and DMSA treated (90 mg/kg for 7 days after lead exposure). After exposure and treatment periods, rats were sacrificed and the brain was separated into cerebellum, hippocampus, frontal cortex, and brain stem; liver, kidney, and blood were also collected. The data indicated a significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) increase in reactive oxygen species (ROS), lipid perioxidation products (LPP), total protein carbonyl content (TPCC), and metal content of brain regions, liver, and kidney in the exposed group compared with their respective controls. In the blood, delta-amino levulinic acid dehydratase (ALAD) activity, RBC, WBC, hemoglobin, and hematocrit showed significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) decrease on lead exposure. However, administration of M. oleifera restored all the parameters back to control, tissue-specifically, and also showed improvement in restoration better than DMSA treatment, indicating reduction of the negative effects of lead-induced oxidative stress.

Biological Trace Element Research, 2014
Lead exposure is known to cause apoptotic neurodegeneration and neurobehavioral abnormalities in ... more Lead exposure is known to cause apoptotic neurodegeneration and neurobehavioral abnormalities in developing and adult brain by impairing cognition and memory. Coriandrum sativum is an herb belonging to Umbelliferae and is reported to have a protective effect against lead toxicity. In the present investigation, an attempt has been made to evaluate the protective activity of the hydroalcoholic extract of C. sativum seed against lead-induced oxidative stress. Male Wistar strain rats (100-120 g) were divided into four groups: control group: 1,000 mg/L of sodium acetate; exposed group: 1,000 mg/L lead acetate for 4 weeks; C. sativum treated 1 (CST1) group: 250 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure; C. sativum treated 2 (CST2) group: 500 mg/kg body weight/day for seven consecutive days after 4 weeks of lead exposure. After the exposure and treatment periods, rats were sacrificed by cervical dislocation, and the whole brain was immediately isolated and separated into four regions: cerebellum, hippocampus, frontal cortex, and brain stem along with the control group. After sacrifice, blood was immediately collected into heparinized vials and stored at 4 °C. In all the tissues, reactive oxygen species (ROS), lipid peroxidation products (LPP), and total protein carbonyl content (TPCC) were estimated following standard protocols. An indicator enzyme for lead toxicity namely delta-amino levulinic acid dehydratase (δ-ALAD) activity was determined in the blood. A significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) increase in ROS, LPP, and TPCC levels was observed in exposed rat brain regions, while δ-ALAD showed a decrease indicating lead-induced oxidative stress. Treatment with the hydroalcoholic seed extract of C. sativum resulted in a tissue-specific amelioration of oxidative stress produced by lead.
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Papers by Prabhakara Yallapragada