Laboratorio Of Toxicologia Ambiental

Massieu, Mexico

Laboratorio Of Toxicologia Ambiental

Massieu, Mexico
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Moreira D.L.,Laboratorio Of Toxicologia Ambiental | Teixeira S.S.,Laboratorio Of Toxicologia Ambiental | Monteiro M.H.D.,Laboratorio Of Toxicologia Ambiental | De-Oliveira A.C.A.X.,Laboratorio Of Toxicologia Ambiental | Paumgartten F.J.R.,Laboratorio Of Toxicologia Ambiental
Brazilian Journal of Pharmacognosy | Year: 2014

In the European Union, traditional herbal medicines that are regarded as "acceptably safe, albeit not having a recognized level of efficacy" fit into a special category of drugs ("traditional herbal medicine products") for which requirements of non-clinical and clinical studies are less rigorous. A regulation proposal published by the Brazilian National Health Surveillance (Anvisa) defines a similar drug category ("traditional phytotherapeutic products") for registration purposes. Regarding herbal medicines, both agencies seem to be lenient regarding proof of efficacy, and consider long-standing folk use as evidence of safety and a waiver of a thorough toxicological evaluation. Nonetheless, several herbal products and constituents with a long history of folk usage are suspected carcinogenic and/or hepatotoxic. Herbal products have also been shown to inhibit and/or induce drug-metabolizing enzymes. Since herbal medicines are often used in conjunction with conventional drugs, kinetic and clinical interactions are a cause for concern. A demonstration of the safety of herbal medicines for registration purposes should include at least in vitroand in vivogenotoxicity assays, long-term rodent carcinogenicity tests (for drugs intended to be continuously used for > 3 months or intermittently for > 6 months), reproductive and developmental toxicity studies (for drugs used by women of childbearing age), and investigation of the effects on drug-metabolizing enzymes. © 2014 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. All rights reserved.


Jimenez-Orozco F.A.,National Autonomous University of Mexico | Rosales A.A.R.,National Autonomous University of Mexico | Vega-Lopez A.,Laboratorio Of Toxicologia Ambiental | Dominguez-Lopez M.L.,Laboratorio Of Inmunobioquimica I | And 5 more authors.
European Journal of Pharmacology | Year: 2011

Esculetin (6,7-dihydroxycoumarin) and daphnetin (7,8-dihydroxycoumarin) are secondary metabolites of plants used in folk medicine. These compounds have showed great antiproliferative activity in several tumor cell lines and have been proposed as potential anticancer agents. However, the estrogenic potential of these two compounds has to date not been reported. The present study compared esculetin and daphnetin on the inhibition of cell proliferation and cell cycle progression of the MCF-7 estrogen-responsive human carcinoma cell line. In vivo and in vitro estrogenic activity for both compounds was also evaluated. Esculetin inhibited cell proliferation after 72 h exposure (IC50 = 193 ± 6.6 μM), while daphnetin evidenced inhibiting effects starting at 24-h exposure (72 h, IC50 = 73 ± 4.1 μM). Both effects showed changes in cyclin D1 gene expression. In non-estrogenic conditions (E-screening assay), esculetin produced biphasic response on proliferation of the MCF-7 cells; at 10 - 8-10 - 6 M, concentrations induced proliferative effects as EC50 = 4.07 × 10 - 9 M (E 2 = 2.91 × 10 - 12 M); at higher concentrations (10 - 5-10 - 4 M), cell proliferation was inhibited. Relative proliferative effect at E 2 was 52% (E 2 = 100), relative proliferative potency was 0.072 (E 2 = 100). Additionally, esculetin tested in vivo showed estrogenic effects at 50-100 mg/kg doses; relative uterotrophic effect at E 2 was 37%, with relative uterotrophic potency registered at 0.003. In contrast, daphnetin did not induce estrogenic effects in vitro or with in vivo models. The low estrogenic activity of esculetin could prove useful in postmenopausal therapy but not as a safe antitumor agent in estrogen-dependent tumors. Daphnetin-based antiproliferative selectivity with MCF-7 cells showed that daphnetin is a promising antitumoral agent also acting on estrogen dependent tumors. © 2011 Elsevier B.V.


PubMed | Instituto Nacional do Cancer INCA, The Broad Institute of MIT and Harvard, Woods Hole Oceanographic Institution and Laboratorio Of Toxicologia Ambiental
Type: | Journal: Marine pollution bulletin | Year: 2017

Pterygoplichthys is a genus of related suckermouth armoured catfishes native to South America, which have invaded tropical and subtropical regions worldwide. Physiological features, including an augmented resistance to organic xenobiotics, may have aided their settlement in foreign habitats. The liver transcriptome of Pterygoplichthys anisitsi was sequenced and used to characterize the diversity of mRNAs potentially involved in the responses to natural and anthropogenic chemicals. In total, 66,642 transcripts were assembled. Among the identified defensome genes, cytochromes P450 (CYP) were the most abundant, followed by sulfotransferases (SULT), nuclear receptors (NR) and ATP binding cassette transporters (ABC). A novel expansion in the CYP2Y subfamily was identified, as well as an independent expansion of the CYP2AAs. Two expansions were also observed among SULT1. Thirty-two transcripts were classified into twelve subfamilies of NR, while 21 encoded ABC transporters. The diversity of defensome transcripts sequenced herein could contribute to this species resistance to organic xenobiotics.


Vega-Lopez A.,Laboratorio Of Toxicologia Ambiental | Carrillo-Morales C.I.,Laboratorio Of Toxicologia Ambiental | Olivares-Rubio H.F.,Laboratorio Of Toxicologia Ambiental | Lilia Dominguez-Lopez M.,Laboratorio Of Inmunoquimica I | Garcia-Latorre E.A.,Laboratorio Of Inmunoquimica I
Archives of Environmental Contamination and Toxicology | Year: 2012

Halomethanes (HMs) are produced autochthonously in water bodies through the action of ultraviolet light in the presence of HM precursors, such as dissolved organic carbon and halogens. In mammals, toxic effects induced by HMs are diverse and include oxidative stress, which is also induced by divalent and polyvalent metals; however, in fish little information is available on HM metabolism and its possible consequences at the population level. In the present study, high CYP 2E1 and GST theta-like activities were found in viscera of the Toluca silverside Chirostoma riojai from Lake Zumpango (LZ; central Mexico). Formaldehyde, one of the HM metabolites, was correlated with CYP 2E1 activity and also induced lipid peroxidation in viscera. Hepatic CYP 2E1 activity was correlated with GST theta-like activity, suggesting the coupling of both pathways of HM bioactivation and its consequent oxidative damage. Sediment metals, among others, were also responsible for oxidative stress, particularly iron, lead, arsenic and manganese. However, under normal environmental conditions, the antioxidant enzymes of this species sustain catalysis adapted to oxidative stress. Findings suggest that this fish species apparently has mechanisms of adaptation and recovery that enable it to confront toxic agents of natural origin, such as metals and other substances formed through natural processes, e.g., HMs. This has allowed C. riojai to colonize LZ despite the high sensitivity of this species to xenobiotics of anthropogenic origin. © Springer Science+Business Media, LLC 2011.


Dzul-Caamal R.,Laboratorio Of Toxicologia Ambiental | Dominguez-Lopez M.L.,Laboratorio Of Inmunoquimica I | Olivares-Rubio H.F.,Laboratorio Of Toxicologia Ambiental | Garcia-Latorre E.,Laboratorio Of Inmunoquimica I | Vega-Lopez A.,Laboratorio Of Toxicologia Ambiental
Ecotoxicology | Year: 2014

In fish, a number of studies have linked acetylcholinesterase (AChE) inhibition with exposure to organophosphate pesticides (OPs); however, evidence suggests the need to study aspects related to the bioactivation and detoxification of OPs, since their neurotoxicity is dependent on these processes. Thus, the study aim was to examine the relations between chlorpyrifos (CPF) and diazinon (DZN) bioactivation by hepatic CYP450 izoenzymes (CYP 2B6, CYP 2C19, CYP 3A4) and detoxification by aryl esterases and oxonases with brain and muscle AChE activity in Chirostoma jordani from three lakes with low to high OPs contamination in water and sediments. We found two patterns of bioactivation in vitro: (i) in fish from a lake with high CPF pollution, the main isoenzymes involved in this process were CYP 2C19>CYP 2B6>CYP 3A4, and (ii) in fish captured in a lake with a high concentration of DZN, the isoenzymes were CYP 3A4>CYP 2C19>CYP 2B6. Bioactivation is shown in this study to be fundamental in brain and muscle AChE inhibition in vivo. The rate of bioactivation of CPF was lower than for DZN. CPF bioactivation was accompanied by reduced detoxification and higher neurotoxicity, which was inversely dependent on the environmental contamination of CPF. Detoxification was also inversely correlated with environmental contamination by CPF, and was higher with diazoxon than chlorpyrifos-oxon. Oxonases were the most relevant enzymes involved in detoxification. The current findings suggest a series of strategies between the bioactivation and detoxification of OPs that allowed the survival of C. jordani despite of OPs pollution levels. © Springer Science+Business Media 2014.


Coelho D.R.,Laboratorio Of Toxicologia Ambiental | Miranda E.S.,Laboratorio Of Toxicologia Ambiental | Saint'Pierre T.D.,Pontifical Catholic University of Rio de Janeiro | Roma Paumgartten F.J.,Laboratorio Of Toxicologia Ambiental
Memorias do Instituto Oswaldo Cruz | Year: 2014

Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.


Paumgartten F.J.R.,Laboratorio Of Toxicologia Ambiental | de Souza N.R.,Laboratorio Of Toxicologia Ambiental
Ciencia e Saude Coletiva | Year: 2013

The use of thalidomide was never discontinued in Brazil where it is prescribed for leprosy type 2 reaction. Babies with birth defects compatible with the thalidomide embryopathy phenotype were born after 1965, an indication that control on drug dispensing and use failed in the country. The article reports data on thalidomide dispensing and clinical uses in the Federal District in 2011/12, when new rules were put into effect, and data on drug dispensing and use obtained ten years earlier. It was found that the number of patients making use of thalidomide declined from 819 in 2001 to 369 in 2011/12. Leprosy accounted for over 70% of prescriptions in both time periods analyzed in this study. In the same time interval, however, use for lupus erythematosus decreased from 13.7 to 4.9%, while that for multiple myeloma increased from 2.9 to 20.3% of all prescriptions. Thalidomide prescription for the remaining approved indications was far less frequent, and so was the use for off label indications that accounted for <1% of prescriptions in 2001 and 2011/12. Registration of prescribing doctors, patients and dispensing units at the state department of health, apparently rendered this control more effective and reliable.


Vega-Lopez A.,Laboratorio Of Toxicologia Ambiental | Ayala-Lopez G.,Laboratorio Of Toxicologia Ambiental | Posadas-Espadas B.P.,Laboratorio Of Toxicologia Ambiental | Olivares-Rubio H.F.,Laboratorio Of Toxicologia Ambiental | Dzul-Caamal R.,Laboratorio Of Toxicologia Ambiental
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology | Year: 2013

The phytoplankton is the basis of food webs and also, may bioconcentrate different toxic substances. This phenomenon is well documented, but there are few studies on the toxic effects on the phytoplankton community. In the current study the relation of oxidative stress (TBARS, ROOH, RC = O) and antioxidant defenses (activities of SOD, CAT, GPx and GST) of two phytoplankton communities with BCF of heavy metals (Cu, Fe, Mn, Pb, Zn) and of PAHs (naphthalene, pyrene, indenol, benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene) was tested. Three sampling surveys were conducted bimonthly on the surface and bottom at different sampling points in the lakes Menor and Mayor of the 2nd section of Chapultepec Park. Also negative and positive controls obtained in the laboratory were included. Toxicity relationships were analyzed using the integrated biomarker response (IBR). Both green algae and cyanobacteria dominated. The contents of ROOH and protein oxidation assessed as RC = O were higher in the Lago Menor, a water body that contains ancient sediments. Through the IBR it was demonstrated that these damages were influenced by Pb, indenol and benzo[b]fluoranthene. In contrast, TBARS content was higher in Lago Mayor, which has sediment in formation. Through IBR it was estimated that Cu, Fe, Mn, Pb, indenol and benzo[b]fluoranthene were related to this damage. However, oxidative stress was accompanied by an induction of CAT and SOD, in contrast, GPx and GST had low or null activity. The field data were similar to the positive controls. We demonstrated for the first time that, although the phytoplankton suffers oxidative stress elicited by metals and PAHs, this community is able to counter this damage through antioxidant defenses. The effects of organic or inorganic toxics in phytoplankton depend on their bioavailability that is modulated by the sediment and also by its physicochemical properties and the characteristics of the abiotic medium. © 2013 Elsevier Inc.


Paumgartten F.J.R.,Laboratorio Of Toxicologia Ambiental
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2010

The relevance of fetal abnormalities noted at maternally toxic doses is a long-standing issue regarding the interpretation of findings of segment II studies. A number of diseases and conditions during pregnancy are known to adversely affect embryo/fetal development, and along this line many scientists believe that any marked disturbance of maternal homeostasis produced by chemical exposure may eventually produce a teratogenic effect. Although there is little doubt that developmental toxicity may be maternally mediated, the notion that, in principle, any maternal toxicity leads to birth defects is disputed. When embryotoxicity is noted only within the maternally toxic dose range, it is not possible to ascertain whether it is in fact maternally mediated or not (i.e., embryo development may have been impaired by a direct action of the chemical at doses that also adversely affect the mother; in these circumstances it would still be a selective developmental toxicant). However, currently, a chemical is not regarded as a "developmental toxicant" (or "teratogenic agent") if embryotoxicity is apparent only at doses that are also toxic to the mother. In the European Union, developmental hazard identification exerts a strong influence on the classification and labeling of chemicals. In Brazil, registration of any pesticide that proved to be teratogenic in animal studies is strictly forbidden by law (Pesticide Law, Federal Law 7.802, 1989). Therefore, interpretation of findings from developmental toxicity studies in light of maternal toxicity is particularly relevant to regulatory agencies, and becomes even more important when labeling or cutoff decision-making criteria are adopted regarding teratogenicity. © 2010 Taylor & Francis Group, LLC.


Moreira D.A.,Laboratorio Of Toxicologia Ambiental | Furtado C.,Instituto Nacional do Cancer INCA | Parente T.E.,Laboratorio Of Toxicologia Ambiental
Gene | Year: 2015

Mitochondrial genes and genomes have long been applied in phylogenetics. Current protocols to sequence mitochondrial genomes rely almost exclusively on long range PCR or on the direct sequencing. While long range PCR includes unnecessary biases, the purification of mtDNA for direct sequencing is not straightforward. We used total RNA extracted from liver and Illumina HiSeq technology to sequence mitochondrial transcripts from three fish (Ancistrus spp.) and assemble their mitogenomes. Based on the mtDNA sequence of a close related species, we estimate to have sequenced 92%, 95% and 99% of the mitogenomes. Taken the sequences together, we sequenced all the 13 protein-coding genes, two ribosomal RNAs, 22 tRNAs and the D-loop known in vertebrate mitogenomes. The use of transcriptomic data allowed the observation of the punctuation pattern of mtRNA maturation, to analyze the transcriptional profile, and to detect heteroplasmic sites. The assembly of mtDNA from transcriptomic data is complementary to other approaches and overcomes some limitations of traditional strategies for sequencing mitogenomes. Moreover, this approach is faster than traditional methods and allows a clear identification of genes, in particular for tRNAs and rRNAs. © 2015 Elsevier B.V.

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