The effect of insulin induced hypoglycemia on ketoconazole hepatototxicity in rabbit

Background: Hypoglycemia is one of the most common side effect of insulin treatment, it affect liver and can potentiate ketoconazole toxicity. Objectives: To measure effect of ketoconazole on liver enzymes, hypoglycemic oxidative stress and to evaluate if N-acetylcysteine, can modulate this effect. Methods: Thirty five male rabbits were randomly divided into five groups: Group 1: (control group), Group 2:( ketoconazole), Group 3: (insulin), Group 4: ( ketoconazole+ insulin), Groups 5: (ketoconazole + insulin + N-Acetyl cysteine). Animals were sacrificed at day 3. Blood collected for measurement of liver enzymes, and total bilirubin. Malondialdehyde and glutathione were measured in serum and liver. Results: Ketoconazole increased serum and liver malondialdehyde, 0.594 ± 0.17 and 4614.49 ± 1288.00 nmol/gm. Increased aspartate aminotransferase 38.19 ± 17.29 and alkaline phosphatase 29.29 ± 10.2 U/L. Insulin increased serum malondialdehyde 0.522 ± 0.19, alkaline phosphatase 15.77 ± 6.12 U/L and bilirubin 0.56 ± 0.26 mg/dl. Ketoconazole + insulin, increased serum malondialdehyde 0.850 ± 0.16 μmol/l and bilirubin 0.77 ± 0.55 mg/dl. Ketoconazole + insulin increased serum malondialdehyde 0.850 ± 0.16 μmol/l, aspartate amino transferase 54.35 ± 18.34 U/L, alanine amino transferase, 34.74 ± 11.08 U/L, alkaline pohospahtase 30.81 ± 12.4 U/L and bilirubin 2.51 ± 1.55 mg/dl. N-acetylcysteine reduced aspartate aminotransferase 28.12 ± 22.21 U/L, alkaline phosphatase 11.81 ± 3.03 IU/L) and bilirubin 0.39 ± 0.18 mg/dl Conclusion: Hypoglycemia caused hepatotoxicity and oxidative stress and potentiates the toxicity of ketoconazole. N-acetylcysteine partly reverse this hepatotoxicity.