首页 | 本学科首页   官方微博 | 高级检索  
检索        


Effects of acetaminophen on reactive oxygen species and nitric oxide redox signaling in kidney of arsenic-exposed rats
Authors:Chhaya Rani MajhiSaleem Khan  Marie Dennis Marcus LeoAyyasamy Manimaran  Palanisamy SankarSouvendra Nath Sarkar
Institution:Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243 122, Bareilly, Uttar Pradesh, India
Abstract:We examined whether acetaminophen could alter renal oxidative stress induced by arsenic; also whether withdrawal of acetaminophen treatment can increase susceptibility of kidney to arsenic toxicity. Acetaminophen (400 and 1600 mg/kg) was co-administered orally to rats for 3 days after preexposure to arsenic (25 ppm) for 28 days (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II). Acetaminophen enhanced arsenic-induced lipid peroxidation, GSH depletion and ROS production and further decreased superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities. Increased peroxidation did not alter kidney weight, but increased serum urea nitrogen and creatinine. Arsenic did not alter basal, iNOS-mediated NO production or iNOS expression. Arsenic decreased cNOS-mediated NO release and eNOS expression in Phase-II. Acetaminophen increased their expressions and NO production in Phase-I. In Phase-II, arsenic-mediated effects on NO remained mostly unaffected with acetaminophen. Results reveal that acetaminophen enhanced the risk of arsenic-mediated oxidative stress in kidney. Discontinuation of acetaminophen administration also increased the susceptibility of kidney to nephrotoxic effect of arsenic. It appeared ROS were primarily responsible for oxidative stress in both the phases. NO may have a minor role in Phase-I, but does not contribute to redox signaling mechanism in Phase-II.
Keywords:AP  acetaminophen  CMC  carboxymethyl cellulose  cNOS  constitutive nitric oxide synthase  CYP  cytochrome P450  eNOS  endothelial nitric oxide synthase  GPx  glutathione peroxidase  GR  glutathione reductase  GSH  reduced glutathione  iNOS  inducible nitric oxide synthase  LPO  lipid peroxidation  MDA  malondialdehyde  NAPQI  N-acetyl-p-benzoquinoneimine  NO  nitric oxide  NOS  nitric oxide synthase  nNOS  neuronal nitric oxide synthase  &bull  O&minus    superoxide anion radical  OH&bull    hydroxyl radical  RNS  reactive nitrogen species  ROS  reactive oxygen species  SOD  superoxide dismutase
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号