Acetaminophen induced kidney failure in rats: A dose response study

Abstract

Acetaminophen is a commonly used analgesic and antipyretic drug, high doses of which cause hepatic and renal injury. In development and progression of kidney disease research, it is necessary to have a suitable common drug to induce uremia and renal failure of rats. It is also required to select the threshold doses for the said drug; a therapeutic dose and toxic dose for kidney failure using standard guidelines. An acute toxicity of acetaminophen was conducted by the limit test at a dose of 2000 mg kgG1 b.wt., on either sex rats (n = 5) and a main test was conducted by a dose progression factor of 3.2 times as per Organization of Economic Co-Operation and Development guidelines 425. Eighteen male albino rats (n = 18) were divided into three groups, group I served as control, groups II and III rats were administered 175 mg and 550 mg kgG1 b.wt., acetaminophen intraperitoneally for 14 days, respectively. Different parameters were considered to analyze renal failure. Urea, creatinine, GOT, GPT and MDA levels were increased significantly (p<0.05) in group III, compared to groups I and II. Antioxidant enzymes like SOD, catalase and GSH level were decreased significantly (p<0.05) in group III rats, compared to group I and II rats. Increase in blood uremia profile indicated that the higher dose of acetaminophen causes uremia. Increase in the toxicity markers and lipid peroxidation marker enzymes indicate the nephrotoxicity. Histological structures of kidney of group III animals showed a severe disorganization of glomerulus and dilation of renal tubules. These results indicate that intraperitoneal injection of acetaminophen at high dose causes nephrotoxicity and renal cellular damage to experimental rats.