title: Induction of oxidative stress in erythrocytes of male rats subchronically exposed to a mixture of eight metals found as groundwater contaminants in different parts of India.
abstract: Exposure of animals and humans to different metal components through contaminated drinking water can result in a wide range of adverse clinical conditions. Toxicological consequences arising from the concurrent repeated exposure to multiple metal contaminants are not known. The purpose of the present study was to evaluate the oxidative stress-inducing potential of a mixture of eight metals (arsenic, cadmium, lead, mercury, chromium, nickel, manganese, iron), representative of groundwater contamination in different areas of India, in erythrocytes of male rats subchronically exposed to environmentally relevant doses via drinking water. The selection of these metals, as determined by literature survey of groundwater contamination in India, was primarily based on the frequency of their occurrence and contamination level above World Health Organization maximum permissible limit (MPL) in drinking water. Male albino Wistar rats were exposed to the metal mixture at 0, 1, 10, and 100 times the mode concentrations (the most frequently occurring concentration) of the individual metals in drinking water for 90 days. In addition, one group of rats was also exposed to the mixture at a concentration equal to the MPL of individual components. The oxidative stress in erythrocytes was evaluated by assessing the magnitude of malondialdehyde production and reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) after 30, 60, and 90 days of exposure. MPL and 1x dose levels did not cause any changes. The mixture at 10x and 100x doses caused dose- and time-dependent effects. After 30 days, the 10x dose did not cause any changes except increase in SOD activity. The 100x dose increased the activities of SOD, catalase and GR and the GSH level, but caused no alterations in lipid peroxidation (LPO) and GPx activity. After 60 days, the 10x dose did not cause any changes. The 100x dose increased LPO and decreased all the antioxidant parameters, except GSH. After 90 days, both 10x and 100x levels elevated LPO. The 10x dose decreased GSH level and activities of SOD and catalase, but not of GPx and GR, whereas the 100x dose decreased all the antioxidative systems. Overall, the present study demonstrates that the subchronic exposure of male rats to the mixture of metals via drinking water results in induction of oxidative stress and concomitant reduction in antioxidative defense system in erythrocytes at 10 and 100 times the mode concentrations of the individual metals in contaminated groundwater.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122, Uttar Pradesh, India.
authors.forename: S H
authors.initials: SH
authors.lastname: Jadhav
authors.forename: S N
authors.initials: SN
authors.lastname: Sarkar
authors.forename: M
authors.initials: M
authors.lastname: Aggarwal
authors.forename: H C
authors.initials: HC
authors.lastname: Tripathi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004781:Environmental Exposure / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007194:India; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019216:Metals, Heavy / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D004338:Drug Combinations; D019216:Metals, Heavy; D014874:Water Pollutants, Chemical; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione