Toxicodynamics of subacute co-exposure to groundwater contaminant arsenic and analgesic-antipyretic drug acetaminophen in rats

Arsenic is an environmental contaminant, while acetaminophen is an extensively used nonsteroidal analgesic-antipyretic drug. We evaluated whether subacute co-exposure to arsenic and acetaminophen would produce more toxicity than that caused by exposure to either of the xenobiotics in rats. Toxicity was evaluated through changes in body weight, feed consumption, liver weight and microsomal drug-metabolizing enzymes, lipid peroxidation and antioxidants in liver. Arsenic had no effect on body weight and feed consumption. Acetaminophen-mediated decrease in body weight was attenuated in the co-exposed rats. Acetaminophen alone or its co-administration with arsenic decreased feed consumption. Arsenic reduced acetaminophen-mediated increase in the activities of drug-metabolizing enzymes. The co-exposure caused lesser lipid peroxidation than the individual exposure. Arsenic or acetaminophen given alone depleted GSH and decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and these effects remained mostly unaffected after co-exposure. The results suggest that co-exposure to arsenic and acetaminophen may be less hazardous than their independent exposure in rats. (C) 2009 Elsevier Inc. All rights reserved.