Copper Induced Hepatic Toxicity in Male Albino Rats and the Possible Protective Effect of Vitamin D

Background: Copper (Cu), a trace element, is safe to consume at low levels. Copper toxicity is often caused by unintentionally ingesting too much Cu from corroded water pipes and from Cu salt-containing creams for burn treatments due to its antimicrobial properties if applied to large areas of burned skin. Unfortunately, Cu-toxicity can extend up to liver cirrhosis. Vitamin D3 (VitD) is known for its efficient antioxidant, anti-inflammatory effects, antiapoptotic and antifibrotic properties. Aim: the present study is designed to detect the possible protective effect of VitD against the toxic effects of Cu on the liver in rats. Material and Methods: Thirty adult rats were divided into three groups (10 mice each): Control group, Cu Group B received Cu at a dose of 0.03 mg/kg body weight by gastric gavage and VitD+ Cu Group C received Vitamin D3 at a dose of (600 IU daily) 10 IU/ kg daily together with Cu for 14 days. Blood samples were collected to assess liver functions, liver tissue was examined for oxidative markers, histological and immunohistochemical examinations. Results: The Cu group B revealed significant increase in AST, ALT and oxidative stress markers. Light microscopic examination showed disturbed hepatic architecture, ballooning of hepatocytes around widened central vein with less acidophilic cytoplasm, pyknotic nuclei and vacuolation. Hepatic sinusoids were dilated and congested between the rays of hepatic cells with dilated portal tracts and inflammatory cellular infiltration around. Liver sections stained by Masson trichrome detected fibrotic changes with increased fibrotic index. Immunohistochemical study showed increase in the proinflammatory cytokine TNFα and decrease in anti-inflammatory IL-10, while TUNEL technique detected increased number of apoptotic cells. Administration of VitD in group C led to a significant reduction in liver dysfunction and oxidative stress, accompanied by marked improvements in histological, immunohistochemical findings and decreased fibrosis and apoptosis. Conclusion: VitD offers significant protective effects against Cu induced liver damage It has antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic properties on the cellular and functional levels. So, VitD supplementation is recommended either as a therapeutic or a prophylactic measure in liver diseases to reduce OS, alleviate hepatic damage and interrupt the fibrotic process. KEYWORDS: Copper toxicity, Microscopic anatomy of the liver, Oxidative stress, Pathological anatomy of hepatic fibrosis, Vitamin D.