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orally to rats for 3 days after preexposure to arsenic (25 ppm) for 28 days (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II).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.
Published Version
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