title: Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.
abstract: OBJECTIVE
  Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions.
  
  
  METHODS
  The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin.
  
  
  RESULTS
  Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed.
  
  
  CONCLUSIONS
  Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation.
authors.affiliation: Proteomics and Bioinformatics Laboratory, Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
authors.forename: Heena
authors.initials: H
authors.lastname: Tabassum
authors.affiliation: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Waseem
authors.affiliation: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India. Electronic address: sparvez@jamiahamdard.ac.in.
authors.forename: Suhel
authors.initials: S
authors.lastname: Parvez
authors.affiliation: Proteomics and Bioinformatics Laboratory, Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
authors.forename: M Irfan
authors.initials: MI
authors.lastname: Qureshi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000633:toxicity*; D000077150:Oxaliplatin; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D009944:Organoplatinum Compounds; D017382:Reactive Oxygen Species; D000077150:Oxaliplatin
keywords: Biomarkers; Hepatotoxicity; Mitochondria; Oxaliplatin; Oxidative stress