Effects of ketoconazole on physiological function of liver and testis in mice

Abstract

Objective: To investigate the effects of different doses of ketoconazole (KCZ) on the physiological functions of the liver and testis in Kunming mice. Methods: Forty male Kunming mice were randomly divided into four groups (n=10): normal group, KCZ low-dose group (30 mg/kg), medium-dose group (50 mg/kg), and high-dose group (70 mg/kg). The mice in the drug groups were injected subcutaneously (0.1 ml/10 g) with the corresponding dose of KCZ once a day, and the concentrations of KCZ in the KCZ low, middle, and high dose groups were 3 mg/ml, 5 mg/ml and 7 mg/ml respectively, and the normal group was injected with the same amount of normal saline for 3 weeks. The activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) in serum, and γ-glutamyl transpeptidase (γ-GT), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in testicular tissue were measured. HE staining was used to observe the pathological changes of the liver and testis. Results: Compared with the normal group, the activities of AST and ALT were increased significantly (P＜0.01), and the activities of γ-GT, ACP and LDH were decreased markedly in KCZ groups (P＜0.01). KCZ could affect the above indexes in a dose-dependent manner. HE staining showed that the hepatocytes were denatured, arranged loosely, and the cytoplasm was light in color. The lumen of the seminiferous tubules of the testis were enlarged, and the number of spermatogenic cells and sperm at all levels were decreased. Conclusion: KCZ could cause physiological function damage and pathological histological changes of the liver and testis, increase the levels of liver transaminase, reduce the activities of testicular specific enzymes of mice. Besides, the degree of damage was increased with the increase of dose.