title: Alterations of mitochondria in liver but not in heart homogenates after treatment of rats with benznidazole.
abstract: The mitochondrial oxidative phosphorylation system was studied in liver and heart homogenates after treatment of rats with benznidazole. The drug was given by oral gavage to adult female Wistar rats for 9 consecutive days (100 mg benznidazole/kg body weight as a daily dose). The mitochondrial state 4 and state 3 respiration rates, respiratory control, efficiency of oxidative phosphorylation (ADP/O), and ATPsynthase activity were assayed. The results showed that according to all these parameters, the mitochondria in cardiac homogenates were not affected in the rats treated with benznidazole. By contrast, mitochondria in the liver homogenates of drug-treated rats were altered, showing decreased respiratory control and a lower coefficient of ADP/O as a result of an increase in the state 4 respiration rate. These data indicate the possibility of production of an uncoupling factor leading to increased proton leakage through the inner mitochondrial membrane as a result of a 9-day treatment of rats with benzonidazole. The obtained experimental data might at least partly explain the nature of benznidazole toxicity in the liver treated with benznidazole.
authors: Laboratory of Biophysics, School of Physics, Faculty of Sciences, National University of Colombia-Medellin Branch, Antioquia, Colombia darendon@unal.edu.co.
authors: D A
authors: DA
authors: Rendon
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009593:Nitroimidazoles / Q000633:toxicity*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D017208:Rats, Wistar
chemical_list: D009593:Nitroimidazoles; D000244:Adenosine Diphosphate; D025261:Mitochondrial Proton-Translocating ATPases; C009999:benzonidazole
keywords: Benznidazole; heart; liver; mitochondria; mitochondrial respiration; oxidative phosphorylation