title: Effects of acetaminophen on reactive oxygen species and nitric oxide redox signaling in kidney of arsenic-exposed rats.
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orally to rats for 3 days after preexposure to arsenic (25 ppm) for 28 days (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II).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.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243 122, Bareilly, Uttar Pradesh, India.
authors.forename: Chhaya Rani
authors.initials: CR
authors.lastname: Majhi
authors.forename: Saleem
authors.initials: S
authors.lastname: Khan
authors.forename: Marie Dennis Marcus
authors.initials: MD
authors.lastname: Leo
authors.forename: Ayyasamy
authors.initials: A
authors.lastname: Manimaran
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Sankar
authors.forename: Souvendra Nath
authors.initials: SN
authors.lastname: Sarkar
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000378:metabolism; D017931:DNA Primers; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000082:Acetaminophen; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D001151:Arsenic