title: Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.
abstract: The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity.
authors.affiliation: Department of Biochemistry, Maharshi Dayanand University, Rohtak, Haryana, -124001, India.
authors.forename: Chandra
authors.initials: C
authors.lastname: Prakash
authors.affiliation: Department of Biochemistry, Maharshi Dayanand University, Rohtak, Haryana, -124001, India. vksiwach.biochem@mdurohtak.ac.in.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001151:Arsenic
keywords: Arsenic; Biogenesis; Mitochondria; MnSOD; Oxidative stress