Concurrent subacute exposure to arsenic through drinking water and malathion via diet in male rats: effects on hepatic drug-metabolizing enzymes.
Arsenic is a known global groundwater contaminant, while malathion is one of the most widely used pesticides in agriculture and public health practices in the world. Here, we investigated whether repeated exposure to arsenic at the groundwater contamination levels and to malathion at sublethal levels exerts adverse effects on the hepatic drug-metabolizing system in rats, and whether concurrent exposure is more hazardous than the single agent. Male Wistar rats were exposed daily to 4 or 40 ppm of arsenic via drinking water, 50 or 500 ppm of malathion-mixed feed and in a similar fashion co-exposed to 4 ppm of arsenic and 50 ppm of malathion or 40 ppm of arsenic and 500 ppm of malathion for 28 days. At term, toxicity was assessed by evaluating changes in body weight, liver weight, levels of cytochrome P(450) (CYP), cytochrome b (5) and microsomal and cytosolic proteins, and activities of aminopyrine-N-demethylase (ANDM), aniline-P-hydroxylase (APH), glutathione-S-transferase (GST) and uridine diphosphate glucuronosyltransferase (UGT) in liver. Arsenic and malathion alone did not alter body weight and liver weight, but these were significantly decreased in both the co-exposed groups. These treatments decreased the activities of ANDM and APH and the levels of liver microsomal and cytosolic proteins, increased GST activity and had no effect on UGT activity. The effects of exposure to low-dose and high-dose combinations on the activities of either phase I or phase II drug-metabolizing enzymes and protein content were mostly similar to that produced by the respective low and high dose of either arsenic or malathion, except APH activity. The effect of arsenic (40 ppm) on APH activity was partially, but significantly, inhibited by malathion (500 ppm). Results indicate that the body or liver weights and the biochemical parameters were differentially affected in male rats following concurrent subacute exposure to arsenic and malathion, with the co-exposure appearing more hazardous to physical variables based on body or liver weights whilst producing biochemical changes comparable to those caused by the individual agents. From these findings, no specific toxicological interaction between arsenic and malathion can be conclusively generalized.
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India. nsuresh@u.washington.edu.
Suresh Babu
SB
Naraharisetti
Manoj
M
Aggarwal
S N
SN
Sarkar
J K
JK
Malik
D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003573:Cytochrome b Group / Q000378:metabolism*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008294:Malathion / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000633:toxicity*; D014881:Water Supply
D018053:Arsenites; D003573:Cytochrome b Group; D004791:Enzyme Inhibitors; D007306:Insecticides; D017670:Sodium Compounds; C017947:sodium arsenite; D003577:Cytochrome P-450 Enzyme System; D008294:Malathion