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The purpose was to investigate the influence of zinc gluconate (ZnG) supplementation on liver and kidney toxicity induced with ethanol (E) and potentiated by rifampicin (R) addition in rats. The experiment was performed on 4 groups: group 1–control, treated for 6 weeks with saline, 1mL/kg; group 2–E, treated for 6 weeks with ethanol (E), 56%; group 3–E+ R, treated with E for 6 weeks and rifampicin 50mg/kg/day, only in the last 14 days of the experiment; group 4–E+ R+ Zn (same treatment as group 3, but, in the last 14 days, zinc gluconate–ZnG, 10 mg/kg/day was added). All administrations were performed by oral gavage. For groups 2, 3, and 4, the ethanol dose was 6g/kg/day on the first 3 days, then it was increased to 7g/kg/day in the following 3 days, and to 8g/kg/day until the end of the experiment. At the end of the experiment (6 weeks), rats were sacrificed and blood samples were collected for biochemistry determinations. Treatment with E for 6 weeks determined significant increases in liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, gamma-glutamyl transferase and alkaline phosphatase, P< 0.001 group 2 vs. 1 for all mentioned parameters) and renal function impairment (increases in serum urea and creatinine, P< 0.001 and respectively P< 0.05, group 2 vs. 1). The antioxidant defense was also impaired in group 2 vs. 1 (superoxide dismutase and glutathione peroxidase activity decreased, P< 0.05). The addition of rifampicin, 50 mg/kg/day during the last 14 days resulted in further increases in alanine aminotransferase and alkaline phosphatase (P< 0.001, group 3 …