Disruptions to Hepatorenal Systems Following Combined Chronic Stress and Metal Toxicities in Rats

Industrialization has significantly increased human exposure to co-occurring psychological stressors and environmental toxicants, including heavy metal contamination. The combined exposures to chronic stressors and heavy metal exposures are common, but their effects on the kidney and liver are not known. Hence, this study investigates how exposure to heavy metals, manganese (Mn) and nickel (Ni), in combination with a chronic stress paradigm in the rat model, impacts the structural and functional integrity of the kidney and liver. Adult Wistar rats were divided into the control, stress-only, Mn-only, stress + Mn, Ni-only, and stress + Ni groups. The rats were treated intraperitoneally with either vehicle, Mn (25 mg/kg), or Ni (25 mg/kg) with/without a restraint stress paradigm for two weeks. Blood, liver, and kidney samples were collected after sacrifice to measure hematological parameters, perform liver and kidney function tests, perform histological examinations, and assess oxidative stress markers. Our results showed significant liver and kidney damage, evidenced by the increased alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin (total, direct, and indirect), urea, uric acid, and creatinine levels in all treatment groups when compared to the control. Histological examinations revealed cell degeneration and necrosis, as well as glomeruli atrophy, tubular degeneration, and parenchymal disintegration in the liver and kidney, respectively. Also, there was increased lipid peroxidation, accompanied by a concomitant decrease in endogenous antioxidants, such as superoxide dismutase, catalase, and glutathione peroxidase, in the liver and kidney. When combined, these factors lead to severe inflammation, cell degeneration, and necrosis, especially with Ni exposure. In conclusion, this study reveals that co-exposure to stress and metals exacerbated hepatorenal disruptions, likely due to worsened oxidative damage.