Abstract
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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
