title: Cisplatin hepatotoxicity mediated by mitochondrial stress.
abstract: BACKGROUND
  Chemotherapy has long been the keystone of cancer regimen, and comprehensive research has been done on the development of more potent and less toxic anti-cancer agents. Cisplatin (CP) is a potent and extensively used chemotherapeutic agent. There is paucity of literature involving role of mitochondria in mediating CP-induced hepatic toxicity, and its underlying mechanism remains unclear. Oxidative stress is a well-established biomarker of the mitochondrial toxicity.
  
  
  OBJECTIVE
  This study evaluates the dose-dependent effects of CP-induced mitotoxicity under in vitro conditions, using mitochondria from rat liver.
  
  
  METHODS
  The aim of our study was to determine the effect of CP with different concentrations in isolated liver mitochondria as an in vitro model.
  
  
  RESULTS
  CP exposure showed significantly compromised level of non enzymatic and enzymatic antioxidants with higher extent of lipid and protein oxidation. CP also caused significant alterations in the activity of respiratory chain enzymes (complex I-III and V) in liver mitochondria.
  
  
  CONCLUSIONS
  It is suggested that mitochondria can be employed as a model for future investigations of anticancer drug-induced hepatotoxicity under in vitro conditions. Studies with selected pharmaceuticals and nutraceuticals might certainly play a definite role in deciphering cellular and molecular mechanisms of CP-induced hepatotoxicity and its amelioration.
authors: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors: Mohammad
authors: M
authors: Waseem
authors: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors: Monica
authors: M
authors: Bhardwaj
authors: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors: Heena
authors: H
authors: Tabassum
authors: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors: Sheikh
authors: S
authors: Raisuddin
authors: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors: Suhel
authors: S
authors: Parvez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D045222:Electron Transport Chain Complex Proteins; D002945:Cisplatin
keywords: Anti-cancer drugs; antioxidants; biomarkers; oxidative stress; respiratory chain enzymes