Cytotoxicity of monocrotaline in isolated rat hepatocytes: Effects of dithiothreitol and fructose
| Autor: | Diego Perandin, Andrea F. Garcia, Fábio Erminio Mingatto, Larissa C. Alves, Flávia Thomaz Verechia Pereira, Marcos A. Maioli |
|---|---|
| Přispěvatelé: | Universidade Estadual Paulista (Unesp) |
| Rok vydání: | 2011 |
| Předmět: |
Male
Programmed cell death Cytochrome Apoptosis Mitochondria Liver Fructose Dehydromonocrotaline Mitochondrion Toxicology Dithiothreitol chemistry.chemical_compound Adenosine Triphosphate medicine Animals Sulfhydryl Compounds Rats Wistar Monocrotaline Toxicity biology Proteins Glutathione Molecular biology Mitochondria Rats medicine.anatomical_structure Mitochondrial permeability transition pore chemistry Biochemistry Hepatocyte biology.protein Hepatocytes Crotalaria |
| Zdroj: | Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 0041-0101 |
| DOI: | 10.1016/j.toxicon.2011.04.010 |
| Popis: | Made available in DSpace on 2013-09-27T14:52:50Z (GMT). No. of bitstreams: 1 WOS000291833400014.pdf: 494276 bytes, checksum: cca35ad03ced70ef3f259152d13c2100 (MD5) Previous issue date: 2011-06-01 Made available in DSpace on 2013-09-30T19:24:25Z (GMT). No. of bitstreams: 1 WOS000291833400014.pdf: 494276 bytes, checksum: cca35ad03ced70ef3f259152d13c2100 (MD5) Previous issue date: 2011-06-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:34:36Z No. of bitstreams: 1 WOS000291833400014.pdf: 494276 bytes, checksum: cca35ad03ced70ef3f259152d13c2100 (MD5) Made available in DSpace on 2014-05-20T15:34:36Z (GMT). No. of bitstreams: 1 WOS000291833400014.pdf: 494276 bytes, checksum: cca35ad03ced70ef3f259152d13c2100 (MD5) Previous issue date: 2011-06-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Monocrotaline (MCT) is a pyrrolizidine alkaloid present in plants of the Crotalaria species that causes cytotoxicity and genotoxicity, including hepatotoxicity in animals and humans. It is metabolized by cytochrome P-450 in the liver to the alkylating agent dehydromonocrotaline (DHM). In previous studies using isolated rat liver mitochondria, we observed that DHM, but not MCT, inhibited the activity of respiratory chain complex I and stimulated the mitochondrial permeability transition with the consequent release of cytochrome c. In this study, we evaluated the effects of MCT and DHM on isolated rat hepatocytes. DHM, but not MCT, caused inhibition of the NADH-linked mitochondrial respiration. When hepatocytes of rats pre-treated with dexamethasone were incubated with MCT (5 mM), they showed ALT leakage, impaired ATP production and decreased levels of intracellular reduced glutathione and protein thiols. In addition, MCT caused cellular death by apoptosis. The addition of fructose or dithiotreitol to the isolated rat hepatocyte suspension containing MCT prevented the ATP depletion and/or glutathione or thiol oxidation and decreased the ALT leakage and apoptosis. These results suggest that the toxic effect of MCT on hepatocytes may be caused by metabolite-induced mitochondrial energetic impairment, together with a decrease of cellular glutathione and protein thiols. (C) 2011 Elsevier Ltd. All rights reserved. Univ Estadual Paulista, UNESP, Lab Bioquim Metab & Toxicol, BR-17900000 Dracena, SP, Brazil Univ Estadual Paulista, UNESP, Lab Morfofisiol Placenta & Embriao, BR-17900000 Dracena, SP, Brazil Univ Estadual Paulista, UNESP, Lab Bioquim Metab & Toxicol, BR-17900000 Dracena, SP, Brazil Univ Estadual Paulista, UNESP, Lab Morfofisiol Placenta & Embriao, BR-17900000 Dracena, SP, Brazil FAPESP: 04/09882-7 |
| Databáze: | OpenAIRE |
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