Papers by Luis Dominguez Boada
Toxics
Ethanol and medical psychotropics (MPs) are legal psychoactive substances widely consumed in West... more Ethanol and medical psychotropics (MPs) are legal psychoactive substances widely consumed in Western countries that are routinely detected in standard toxicological analyses at compulsory autopsies, and toxicokinetic interactions between these drugs have been described. However, studies assessing the consequences of this co-consumption are scarce in Europe. We performed a retrospective study on toxicological results from compulsory autopsies in Spain. Thirty-five legal psychotropics, including ethanol, were measured in blood samples from 380 decedents to assess the determinants of such co-consumption. MPs were detected in 42.4% of the subjects. Polypharmacy was frequent in our series (25%), being more frequent in men than in women. More than one-third of the decedents had detectable levels of ethanol, and a significant positive association between ethanol levels and age was evident. About one-third of MPs consumers were also co-consumers of ethanol. The simultaneous consumption of e...
Resumen: En el presente estudio se ha evaluado el grado de contaminacion por contaminantes organi... more Resumen: En el presente estudio se ha evaluado el grado de contaminacion por contaminantes organicos persistentes (COPs) en 193 ejemplares de tortuga boba (Caretta caretta) varadas en las Islas Canarias entre 2007-2011. La cuantificacion en plasma de los niveles de pesticidas organoclorados (POCs), bifenilos policlorados (PCBs) e hidrocarburos aromaticos policiclicos (PAHs) se realizo mediante GC-MS. Todas las muestras analizadas presentaron niveles cuantificables de alguno de los COPs incluidos en el estudio. El grupo de COPs que presento mayores niveles fue el de los PAHs (alcanzando la carga total de PAHs 6,45 ng/ml), siendo el fenantreno el hidrocarburo mas frecuentemente detectado y a concentraciones mas altas, lo que indica el origen petrogenico de estos contaminantes. La contaminacion por PCBs alcanzo niveles menores (3,84 ng/ml), predominando el grupo de los hexaclorobifenilos (PCB-153 y PCB138 principalmente). Los niveles de contaminacion por POCs fueron tambien bajos alcan...
Data in Brief, 2021
The dataset presented in this article supports "Intensive livestock farming as a major determinan... more The dataset presented in this article supports "Intensive livestock farming as a major determinant of the exposure to anticoagulant rodenticides in raptors of the Canary Islands (Spain)" (Rial-Berriel et al., 2020). A Geographic Information
Science of The Total Environment, 2019
Heavy metals and other toxic elements are frequently detected in humans. Rare earth elements (REE... more Heavy metals and other toxic elements are frequently detected in humans. Rare earth elements (REE) have arisen as a novel group of substances considered as emerging pollutants due to its dependence for high tech industry. We designed a study aimed to conduct the biomonitoring a total of 45 inorganic elements in the population of Andalusia (Spain). A total of 419 participants were recruited and their plasma samples analyzed. Concentration of elements, including elements in the ATSDR's priority pollutant list and REE were measured by ICP-MS in the blood plasma of participants. Arsenic, copper, lead, selenium, antimony, strontium, and bismuth were detected in ˃98% of subjects. Median values of arsenic, mercury and lead were 1.49, 1.46, and 5.86 ng/mL, respectively. These concentrations did not exceed reference values published by international agencies. We observed a positive correlation between age and plasma concentrations of arsenic, mercury, antimony and strontium. Sum of elements was lower in the group of subjects younger than 45 years old (P = 0.002). Positive correlations were observed between body mass index (BMI) and plasma concentrations of barium, cerium, osmium, tin, and ytterbium. 7 out of 26 REEs showed a percentage of detection ≥ 90%. Bismuth, yttrium, and cerium were quantified at the highest concentrations (median value = 7.7, 0.19, and 0.16 ng/mL, respectively). We found that plasma levels of 6 REEs were higher among males, and a positive correlation between REEs and age was detected. The present results suggest a potential interaction with the human physiology that deserves additional research. Given the high persistence of these elements in the environment, and the significant technological dependence on them, future studies are needed to elucidate the potential sources of exposure and possible adverse effects on health, especially in the most vulnerable populations.
International Journal of Environmental Health Research, 2019
Inorganic elements have been associated with brain tumours for long. The blood concentration of 4... more Inorganic elements have been associated with brain tumours for long. The blood concentration of 47 elements was assessed by ICP-MS in 26 brain tumour patients and 21 healthy subjects from Bucharest (Romania). All 47 elements were detected in the brain tumour tissue, and 22 were detected in > 80% of samples; this implies that these elements can cross the bloodbrain barrier. Median blood levels of cadmium, lead, and nickel were higher than the reference values (1.14, 53.3, and 2.53 ng/mL). Gadolinium and tantalum showed significantly higher concentrations among cases. We observed considerable differences and different profiles of the presence of inorganic elements between the tumour and nontumour brain tissue and between tissue from the primary tumour and tissue from brain metastasis. Our data suggest that similar to heavy metals, other elementscommonly used in high tech devices and rare earth elementscan also influence brain tumour.
Journal of Forensic and Legal Medicine, 2019
The aim of this study was to analyze the prevalence of ethanol in individuals (277) subjected to ... more The aim of this study was to analyze the prevalence of ethanol in individuals (277) subjected to a mandatory medico-legal autopsy in the Institute of Legal Medicine of Las Palmas (Canary Islands, Spain) during 2016-2017, comparing the results with data published in 2015. Blood and/or vitreous humor samples were analyzed by gas chromatography. 31.8% of the individuals were positive to ethanol. We observed a decrease in the prevalence of ethanol among males (p = 0.002). While the prevalence of ethanol was reduced, the concentration among those positive subjects has increased. 11.9% of the series died in a traffic accident and the percentage of positive to ethanol decreased in relation to 2015 (64.3, 25.0, and 35.3%). The number of suicides remains constant, although the age of the suiciders has been significantly reduced (p = 0.022). The results of this study indicate that ethanol is still heavily involved in non-natural deaths.
International Journal of Environmental Health Research, 2018
We conducted a cross-sectional study in the Hospital Universitario de Canarias (Tenerife, Canary ... more We conducted a cross-sectional study in the Hospital Universitario de Canarias (Tenerife, Canary Islands, Spain) measuring 22 inorganic elements in amniotic fluid (AF) samples obtained from 65 pregnant women. ICP-MS was used for quantification of inorganic elements. Newborn parameters at delivery were all within the normal range. Concentrations of all elements were detected in measurable amounts in AF. The concentration of elements was similar to those reported in the literature. The concentrations of the most dangerous heavy metals-Cd, Cr, Ni, Hg and Pbwere lower than those reported by other authors. This study demonstrates that toxic inorganic elements pass into and accumulate in AF. The presence of such pollutants in contact with developing embryos from the intrauterine period could exert adverse health effects that deserve future investigations.
Environmental Research, 2018
Environmental pollution due to various elements is increasing all across the planet owing to thei... more Environmental pollution due to various elements is increasing all across the planet owing to their use in industrial processes. The tobacco plants and the vegetables used in the manufacturing of smoking paper may accumulate these elements from the environment. Thus, tobacco and smoking paper may be relevant contributors among the content of elements in cigarettes, including some emerging pollutants such as rare earth elements (REEs). Thirty-two elements related to hi-tech industrial processes were analyzed in tobacco, rolling paper, and filters (n = 257 samples) by ICP-MS. A variety of industrial brands and "roll-your-own" cigarette papers were considered. The potential maximum daily exposure to these elements by a hypothetical heavy smoker was calculated for each type of cigarette. We found significant differences in the levels of most elements, both in the tobacco and in the paper. Black tobacco cigarettes contained the maximum levels. We found that the paper used in roll-your-own cigarettes may significantly modify their concentration of elements. Fast-burning, bleached, and flavored papers also contribute to higher levels of these pollutants. Thus, the differences in theoretical exposure depending on the type of cigarette consumed-either branded or hand-rolled-may be very striking, of up to 35-40 times. In addition to the number of cigarettes consumed per day, it is necessary to consider the type of cigarette consumed to assess the risk of exposure to toxic elements. Tobacco paper is a prominent source of exposure to toxic elements. Cigarette smoke is another source of exposure to emerging contaminants such as REE.
Environmental Research, 2016
Polychlorinated biphenyls (PCBs) are toxic and persistent chemicals produced between 1930s and 19... more Polychlorinated biphenyls (PCBs) are toxic and persistent chemicals produced between 1930s and 1980s, which accumulate in humans and wildlife. Although a decreasing trend of PCB levels in humans has been described in developed countries, mainly as a consequence of strict regulations and remediation plans, an inverse trend has been recently reported in people from developing countries. We had the opportunity of sampling a series of African immigrants recently arrived to the Spanish archipelago of the Canary Islands, in which high levels of PCBs have been described, and we studied the relationships between their level of contamination and health status. A total of 570 subjects who underwent a complete medical examination and a face-to-face interview were recruited for this study. Hematological and biochemical parameters (blood and urine) were determined in all participants. Serology for the diagnostic of infectious diseases was also performed, and direct identification of parasites was performed in feces, urine or blood samples when appropriate. It is remarkable that up to 26.0% of the population had intestinal parasites, and we found an inverse relationship between PCB levels and parasitism and parasitic diseases: median values of PCBs were lower in parasitized subjects than in subjects without parasites in stool (237.6 ng/g fat vs. 154.4 ng/g fat for marker PCBs, p ¼0.015) and median values of dioxin-like PCBs were lower in subjects carrying pathogen parasites than among subjects showing nonpathogen parasites in stool (0.0 ng/g fat vs. 13.1 ng/g fat, respectively; p¼ 0.001). Although this inverse association had been described in some vertebrates this is the first study reporting such an association in humans. Furthermore, it has been also recently described that PCBs may disrupt iron metabolism, and we found a direct relationship between serum iron and total PCBs burden (r ¼0.231, p¼ 0.025), suggesting that PCBs, although at subclinical level, could play a role on iron homeostasis. Although the role of PCBs in parasitism and in the iron metabolism needs future research, our findings may help to understand the adverse health outcomes associated to environmental exposure to PCBs and they might be used in exposed populations as indicators of subtle effects due to environmental insult.
The Journal of pharmacology and experimental therapeutics, 1994
The present work focuses on the interaction of 17 alpha-ethinyl estrogen derivatives with the [3H... more The present work focuses on the interaction of 17 alpha-ethinyl estrogen derivatives with the [3H]dexamethasone ([3H]DEX) binding site from male rat liver microsomes and the induction of this site by the in vivo administration of natural and synthetic estrogens. [3H]DEX binds to a single-saturating binding site (Kd = 100 nM; maximal binding = 13 pmol/mg of protein) in the liver microsomes. In competition experiments, ethinylestradiol (EE2) and mestranol were able to inhibit [3H]DEX binding to microsomes, whereas natural estrogens, tamoxifen or estrogen sulfates were ineffective. Saturation analysis performed by incubating [3H]EE2 with liver microsomes revealed the existence of a low-affinity (Kd = 280 +/- 30 nM) and high capacity (maximal binding = 16 +/- 2 pmol/mg of protein) binding site. Saturation, competition and dissociation experiments suggest that [3H]DEX and [3H]EE2 interact with the same microsomal entity. Synthetic and natural estrogens increased the hepatic expression of...
Archives of Toxicology, 2001
The aim of this study was to evaluate the acute hepatic effects exerted by the steroid hormone pr... more The aim of this study was to evaluate the acute hepatic effects exerted by the steroid hormone progesterone (PR) in the rat. Although the liver is not a target tissue for this hormone, a number of hepatic actions of PR have been described, and, furthermore, a specific binding site for PR (PBS) exists in rat liver microsomes. Immature male rats were treated intraperitoneally with 60 mg/kg PR per day for 1, 5 or 10 days, and different parameters were evaluated in order to detect possible alterations in liver cells. Morphological study of the livers did not present images of cytotoxicity in any group of animals. The presence of a clear hyperplasia of smooth endoplasmic reticulum (SER) was noteworthy, mainly seen in perilobular hepatocytes. Despite this SER increase, the levels of cytochrome P450 (Cyt P450) significantly decreased after 10 days of PR administration. Similarly, the concentration of PBS was significantly decreased after 10 days of treatment with PR. On the other hand, these studies revealed a clear increase of mitotic activity and Ki-67 labelling index in the livers of animals treated with PR; furthermore, livers of PRtreated animals showed an increased percentage of binucleate hepatocytes. Flow cytometry analysis showed that although ploidy status of liver cells was not modified in any case the percentage of diploid nuclei in Sphase decreased during treatment with PR. The most relevant finding was the presence of abnormal mitosis and c-mitosis in livers from animals from all PR-treated groups. This study demonstrates that PR (a) does not induce cytotoxicity although it can induce cell proliferation and spindle disturbances in liver cells, (b) may also modulate the drug-metabolizing liver enzyme function, and (c) downregulates the expression of its own microsomal specific binding site.
Science of The Total Environment, 2005
Environmental Toxicology and Pharmacology, 2007
Our multigenerational study evaluates the hepatic effects of the xenoestrogens nonylphenol (NP), ... more Our multigenerational study evaluates the hepatic effects of the xenoestrogens nonylphenol (NP), and 4-octylphenol (4OP) on male and female rats when they are exposed uninterruptedly, from conception to adult age, to tap water containing 25 ppm of NP or 4OP. Our results showed that these compounds did not induce any change in liver/body weight ratio (relative liver weight, RLW). In the morphological analysis we did not find evident signs of cytotoxicity. The most relevant findings were the presence of both an increase in the apoptotic index and in the percentage of binuclear hepatocytes in livers from exposed animals. Additionally, our study revealed the presence of hepatocellular glycogenosis (mainly in 4OP-exposed rats): the type of glycogen accumulated was in aggregates (gamma-glycogen), a non-functional form of glycogen. This study demonstrates that, at levels close to those described in the environment, NP and 4OP are capable of inducing a number of hepatic effects, potentially related with adaptive, and/or metabolic alterations of liver tissue.
Endocrinology, 1994
Some 17 alpha-alkylated androgens used as anabolic agents, such as stanozolol (ST) and danazol (D... more Some 17 alpha-alkylated androgens used as anabolic agents, such as stanozolol (ST) and danazol (DA), have specific effects on the liver that are not exerted by testosterone. This gives rise to the possibility that a steroid-binding protein, other than the androgen receptor, could modulate the intracellular actions of these agents. Male rat liver microsomes contain a homogeneous population of [3H]dexamethasone ([3H]DEX)-binding sites which we have denominated low affinity glucocorticoid-binding sites (LAGS). Because glucocorticoids, progestagens, and the synthetic estrogen ethynyl estradiol compete with [3H]DEX for binding to the LAGS, we aimed to study the possible interactions between androgens and the LAGS. To investigate whether several androgens had the capability of interacting with the LAGS, we performed competition experiments. The LAGS had no affinity for testosterone or methyltrienolone (R1881). However, some 17 alpha-alkylated androgens (DA (IC50, 116 nM) > ST > fluoxymesterone > mestaline > methandriol > methandrostenolone > methyltestosterone) were able to compete with [3H]DEX binding to liver microsomes. ST and DA were potent inhibitors of [3H]DEX binding to liver microsomes. They decreased both the affinity and the number of [3H]DEX-binding sites, increased the dissociation rate of [3H]DEX from the LAGS, and provoked a time- and dose-dependent inactivation of the [3H]DEX-binding site. These results strongly suggest that ST and DA exert a negative allosteric modulation on [3H]DEX binding to the LAGS. The in vivo administration of ST (but not other androgens) to male rats provoked a time- and dose-dependent decrease in the LAGS level. Full recovery of the LAGS concentration required at least 8 h and was blocked by protein synthesis inhibitors. Such results suggest that ST irreversibly inactivates the [3H]DEX-binding site in vivo as it does in vitro. Taken together, these observations are indicative of an irreversible interaction between some 17 alpha-alkylated androgens and the LAGS both in vitro and in vivo and suggest that ST may be an important pharmacological tool that can be used in the elucidation of the molecular structure of the LAGS. These results also mean that the LAGS are a steroid-binding entity able to distinguish between natural androgens and 17 alpha-alkylated testosterone derivatives used as anabolic agents.
British Journal of Sports Medicine, 2005
Anabolic androgenic steroids (AAS) are used illicitly at high doses by bodybuilders. The misuse o... more Anabolic androgenic steroids (AAS) are used illicitly at high doses by bodybuilders. The misuse of these drugs is associated with serious adverse effects to the liver, including cellular adenomas and adenocarcinomas. We report two very different cases of adult male bodybuilders who developed hepatocellular adenomas following AAS abuse. The first patient was asymptomatic but had two large liver lesions which were detected by ultrasound studies after routine medical examination. The second patient was admitted to our hospital with acute renal failure and ultrasound (US) studies showed mild hepatomegaly with several very close hyperecogenic nodules in liver, concordant with adenomas at first diagnosis. In both cases the patients have evolved favourably and the tumours have shown a tendency to regress after the withdrawal of AAS. The cases presented here are rare but may well be suggestive of the natural course of AAS induced hepatocellular adenomas. In conclusion, sportsmen taking AAS ...
Archives of Toxicology, 1999
Stanozolol (ST) is a 17a-alkyl anabolic-androgenic steroid (17a-AAS) often misused by athletes an... more Stanozolol (ST) is a 17a-alkyl anabolic-androgenic steroid (17a-AAS) often misused by athletes and bodybuilders. The use of anabolic-steroids by sportsmen and teenagers has increased dramatically, thus raising the question about their hepatotoxicity, specially those such as ST which are orally administered. Previously, we have reported diverse in vivo eects exerted by this steroid and published the existence of a highly speci®c ST-binding site in male rat liver microsomes. The existence of this binding site, the reported hepatic eects exerted in humans, and the very limited information about its potential hepatotoxicity led us to treat adult male rats acutely and chronically with ST and study dierent parameters that could indicate liver damage: serum levels of transaminases, concentration of monooxygenase enzymes in liver, liver membrane lipid peroxidation products, liver histopathology, and cell cycle/ploidy status of liver cells. In our study, no changes in serum transaminases or lipid peroxidation levels were obtained. However, acute stanozolol treatment signi®cantly decreased the levels of cytochrome P450 (Cyt. P450) and cytochrome b 5 (Cyt. b 5) during the ®rst 48 h of treatment, while subsequently, at 72 and 96 h, these microsomal enzymes underwent a signi®cant increase in their levels. In sharp contrast with this response to acute treatment, the content of these two enzymes during chronic treatment showed an important decrease. Interestingly, acutely and chronically ST-treated livers showed slight to moderate in¯ammatory or degenerative lesions in centrilobular hepatocytes. Flow cytometric analysis demonstrated that both acute and chronic ST treatment were capable of increasing the percentage of S-phase fraction (%SPF) of liver cells. These ®ndings taken together clearly show that this steroid is capable of altering the liver capacity for metabolizing xenobiotics and indicate that high doses of ST could exert a proliferative eect on liver cells. Such data should be considered in risk evaluations for this compound.
Toxics, 2022
Medical psychotropics are widely used and prescribed in developed countries. These medications ma... more Medical psychotropics are widely used and prescribed in developed countries. These medications may have an impairing effect on mood or perception and may induce harmful behaviors. Nevertheless, in Europe, studies on their importance from a medico-legal perspective are scarce. To fill this gap, we evaluate the determinants of these drugs in a retrospective study based on data obtained from forensic autopsies. Toxicological analyses were performed on 394 blood samples from compulsory autopsies at the Institute of Legal Medicine of Las Palmas. Of the samples, 41% (159) were positive for at least one psychotropic, with benzodiazepines being the most frequently detected (24.1%), followed by opiates and antidepressants. Benzodiazepines, opiates, and antidepressants were detected more frequently in men who suffered a violent death. More than 30% of the positive samples showed two or more drugs, suggesting a prevalence of polypharmacy among forensic autopsy subjects, with the most frequentl...
Toxics, 2021
Dry feed for pets lacks specific legislation regarding maximum residue limits for inorganic eleme... more Dry feed for pets lacks specific legislation regarding maximum residue limits for inorganic elements. The aim of the present study was to determine the content of 43 inorganic elements in dog and cat feed, studying whether there were differences according to the supposed quality of the food and performing the risk assessment for health. Thirty-one and thirty packages of pelleted dry food for cats and dogs, respectively, were analyzed. After acidic microwave-assisted digestion, elements were detected and quantified by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In general, we did not observe important differences in the content of elements according to the supposed quality of the brand. Among trace elements, selenium and manganese are above the dietary reference value. Arsenic and mercury showed the highest acute hazard indexes, which make them risk factors for the health of dogs and cats. Aluminum, uranium, antimony and vanadium contents were above the toxic reference val...
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Papers by Luis Dominguez Boada