Abstract
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.
Highlights
Hypoglycemia is a common dangerous side effect of insulin therapy
The level of AST was significantly increased in the group treated with the combination of in comparison to the group treated with insulin alone group P < 0.05
MDA levels in serum and liver homogenate increased in the insulin group and this reflects the increasing levels of lipid peroxidation and free radicals generation which may lead to tissue damage, mitochondrial failure, cell death [14] and impairment of endogenous antioxidants defense mechanisms.[15]
Summary
Hypoglycemia is a common dangerous side effect of insulin therapy. Failure of glucose supply to the brain causes progressive cognitive impairment, and coma.[1]. Hypoglycemia is one of the most common side effect of insulin treatment, it affect liver and can potentiate ketoconazole toxicity. 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.
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