Navegando por Palavras-chave "Hepatotoxicity"

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    Estudo de associação entre polimorfismos dos genes ERCC1 e ABCB1 e nefro-hepatotoxicidade à quimioterapia com Paclitaxel/Carboplatina em pacientes com câncer ginecológico
    (Universidade Federal de São Paulo (UNIFESP), 2020-03-05) Costa Junior, Luiz Carlos Da [UNIFESP]; Santos, Paulo Caleb Junior De Lima [UNIFESP]; Vianna-Jorge, Rosane [UNIFESP]; http://lattes.cnpq.br/7806610722907256; http://lattes.cnpq.br/7270343730265469; http://lattes.cnpq.br/1669800539285831; Universidade Federal de São Paulo
    Background: Paclitaxel/carboplatin combination is the standard chemotherapeutic protocol for gynecological cancers, but severe toxicities such as nephro and hepatotoxicity may compromise treatment. There is great interindividual variability regarding the incidence and severity of toxicities, which may be accounted to single nucleotide polymorphisms (SNPs) affecting drug transport or cellular sensitivity. Objective: To evaluate the impact of selected SNPs in ERCC1 and ABCB1 genes on the incidence of nephro- and hepatotoxicity in patients with gynecological cancer treated with paclitaxel/carboplatin. Methods: A cohort of 507 gynecological cancer patients receiving paclitaxel/carboplatin from the Brazilian National Cancer Institute (INCA-Brazil). Clinical data were obtained during routine consults or at electronic medical records. Hepatic and renal toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). Genotyping was performed using real-time PCR. Results: ABCB1 c.1236C>T was associated with moderate to severe (grades 2- 4) nephrotoxicity (OR: 2.40; 95% CI 1.39–4.15), whereas ERCC1 c.118C>T was associated with moderate to severe hepatotoxicity (OR 3.71; 95% CI 1.08– 12.77). Conclusions: ABCB1 c.1236C>T and ERCC1 c.118C>T can be potential biomarkers for the risk of nephro- and hepatotoxicity to carboplatin/paclitaxel chemotherapy of gynecological cancers.
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    Modelo experimental de indução de lesão oxidativa hepática em ratos por halotano
    (Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia - IBEPEGE Colégio Brasileiro de Cirurgia Digestiva - CBCD Sociedade Brasileira de Motilidade Digestiva - SBMD Federação Brasileira de Gastroenterologia - FBGSociedade Brasileira de Hepatologia - SBHSociedade Brasileira de Endoscopia Digestiva - SOBED, 2007-03-01) Brasil, Luis Josino; Amaral, José Luiz Gomes do [UNIFESP]; Zettler, Claudio Galeano; Marroni, Claudio Augusto; Vercelino, Rafael; Marroni, Norma; Irmandade da Santa Casa de Misericórdia de Porto Alegre Serviço de Anestesiologia; Universidade Federal de São Paulo (UNIFESP); Fundação Faculdade de Ciências Médicas de Porto Alegre Departamento de Patologia; Fundação Faculdade de Ciências Médicas de Porto Alegre Departamento de Hepatologia; Universidade Federal do Rio Grande do Sul Hospital das Clínicas de Porto Alegre Laboratório de Fisiologia Experimental
    BACKGROUND: The anesthetic halothane can be reductively metabolized to reactives intermediates that may initiate lipid peroxidation accompanied by hepatic injury. Hypoxia and phenobarbital pretreatment in rats increases metabolism of halothane, the oxidative stress, cause liver antioxidant enzymes changes and tissue damage. AIMS: We investigated the effect of halothane on hepatic lipid peroxidation and on hepatic histology after increases reductive metabolism of halothane caused by hypoxia and phenobarbital pretreatment. METHODS: Twenty-five male wistar rats were divided in five equals groups: CO (Control), HO14 (Halothane/Hypoxia), F (fenobarbital alone), O14 (Hypoxia alone) and H (Halothane alone). After 24 hours the rats were killed, their livers removed to determine chemoluminescence, thiobarbituric acid-reactive substances, catalase, superoxide dismutase, and blood samples were taken to determine AST and ALT. The histopathologic evaluation was performed with hematoxylin and eosin staining. Histopathologic scores are presented as 25th-75th percentile/range values and median ± range. RESULTS/CONCLUSION: Halothane-hypoxic exposure resulted in a significant changes in the activities of antioxidant enzymes, and induced hepatic lipoperoxidation. Moreover it resulted in histopathologic liver injury as well as significant increase of serum activity of AST and ALT.
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    On the mechanisms of phenothiazine-induced mitochondrial permeability transition: Thiol oxidation, strict Ca2+ dependence, and cyt c release
    (Elsevier B.V., 2010-10-15) Cruz, Thiago S.; Faria, Priscila A.; Santana, Debora P.; Ferreira, Juliana C. [UNIFESP]; Oliveira, Vitor [UNIFESP]; Nascimento, Otaciro R.; Cerchiaro, Giselle; Curti, Carlos; Nantes, Iseli L.; Rodrigues, Tiago; UMC; Universidade Federal do ABC (UFABC); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Phenothiazines (PTZ) are drugs widely used in the treatment of schizophrenia. Trifluoperazine, a piperazinic PTZ derivative, has been described as inhibitor of the mitochondrial permeability transition (MPT). We reported previously the antioxidant activity of thioridazine at relatively low concentrations associated to the inhibition of the MPT (Brit. J. Pharmacol., 2002;136:136-142). in this study, it was investigated the induction of MPT by PTZ derivatives at concentrations higher than 10 mu M focusing on the molecular mechanism involved. PTZ promoted a dose-response mitochondrial swelling accompanied by mitochondrial transmembrane potential dissipation and calcium release, being thioridazine the most potent derivative. PTZ-induced MPT was partially inhibited by CsA or Mg2+ and completely abolished by the abstraction of calcium. the oxidation of reduced thiol group of mitochondrial membrane proteins by PTZ was upstream the VIP opening and it was not sufficient to promote the opening of PTP that only occurred when calcium was present in the mitochondrial matrix. EPR experiments using DMPO as spin trapping excluded the participation of reactive oxygen species on the PTZ-induced MPT. Since 117 give rise to cation radicals chemically by the action of peroxidases and cyanide inhibited the PTZ-induced swelling, we propose that VIZ bury in the inner mitochondrial membrane and the chemically generated 117 cation radicals modify specific thiol groups that in the presence of Ca2+ result in MPT associated to cytochrome c release. These findings contribute for the understanding of mechanisms of MET induction and may have implications for the cell death induced by PTZ. (C) 2010 Elsevier Inc. All rights reserved.
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    Toxicidade reprodutiva, mutagenicidade, genotoxicidade e citotoxicidade do Arsênio em ratos machos expostos durante o desenvolvimento pré-puberal
    (Universidade Federal de São Paulo (UNIFESP), 2019-05-09) Samelo, Ricardo Rodrigues [UNIFESP]; Perobelli, Juliana Elaine [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Arsenic (As) is an element that naturally occurs in the environment and can contaminate air, soil, water and organisms by mobilizing its natural mineral deposits. In addition, contamination may result from anthropogenic activities such as industrial processes, mining and metallurgy. Inorganic compounds are generally more toxic and are widely available in aquatic environment, including sources of drinking water. Studies have shown that more than 150 million people worldwide are affected by concentrations above 0.01mg/L of As in drinking water, which corresponds to the tolerable limit according to World Health Organization. Plants and animal organisms from contaminated sites are the main sources of intoxication for the general population through diet intake. The toxicity of As is related to the endogenous production of oxygen and nitrogen reactive species. The present study investigated whether exposure to inorganic arsenic during male pre-pubertal development causes reproductive toxicity, genotoxicity, mutagenicity and cytotoxicity in rats. In this study, male Wistar rats (21 days old) were distributed into 3 groups (n = 10/group): control (vehicle, filtered drinking water), As1 (AsNaO2 0.01mg.L-1) and As2 (received AsNaO 2 at 10 mg.L-1). The animals were treated from postnatal day 23 to 53, when they were euthanized. Damage to reproductive system was observed in As-treated animals when compared to control, both in the testes and in the epididymis, indicating impairment on spermatogenic process and sperm maturation. The liver has been shown to be an important target tissue for As toxicity in animals exposed to As in these experimental conditions, presenting defense cell infiltrates, DNA damage and increased rates of apoptosis. In the renal tissue an As exposition did not showed visible alterations in histological analysis. The micronucleus test in bone marrow reveled a bigger amount of micronucleated cells in As1. However, the Cometa assay to evaluate genotoxicity did not demonstrated difference between the experimental groups. Mass spectrometry revealed higher concentrations of As in testis, epididymis, kidney and liver of As2 group compared to As1 and Control. In conclusion, Inorganic As exposure during prepubertal development causes reproductive toxicity, mutagenicity and cytotoxicity in male rats.