Evaluation of hepatorenal impairments in Wistar rats coexposed to low-dose lead, cadmium and manganese: insights into oxidative stress mechanism.

The study aims to evaluate effects of chronic low-dose coexposure to lead (Pb), cadmium (Cd) and manganese (Mn) on hepatorenal toxicity and oxidative stress. Young male Wistar rats were treated with Pb acetate (1.4 mg/kg BW), Cd chloride (0.01 mg/kg BW), Mn chloride (0.14 mg/kg BW) and their combination (Pb + Cd + Mn) by oral gavage, for 15 weeks. Liver enzymes, albumin (Alb), globulin (Glb), total protein, creatinine, urea and electrolyte concentrations were measured in the serum. Hepatic and renal malondialdehyde (MDA), glutathione peroxidase-1 (GPx1) and metallothionein-1 (MT1) concentrations were measured by enzyme immunoassay technique. Chronic exposure to the metals significantly (p < .05) increased serum Glb concentration and decreased Alb/Glb ratio, compared to the controls. Serum creatinine concentration significantly (p < .05) decreased in the Pb, Cd and Pb + Cd + Mn groups, but elevated in the Mn group. Hepatic MDAs rose significantly (p < .05) in the Pb group, while hepatic GPx1 activities increased significantly (p < .05) in the Cd, Mn and Pb + Cd + Mn groups. Hepatic and renal MT1 concentration decreased (p < .05) in the Mn group only. Biochemical alterations were confirmed by light microscopy of the liver and kidneys, which showed degenerative changes. It is concluded that prolonged coexposure to environmentally relevant levels of Pb, Cd and Mn impairs liver and kidney functions via the induction of oxidative stress, and it underlines the importance of studying toxicants in combination.