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Go to Editorial ManagerMitoxantrone is a chemotherapeutic very effective against a variety of human malignancies Administration of Mitoxantrone is associated with hepatotoxicity Zinc has protective effect in liver illness. This study aimed to determine the role of zinc gluconate as a hepatoprotective agent in Mitoxantrone induced hepatotoxicity in rats. Methods there were twenty-four male and female rats used. Rats were divided up Into three groups, each consisting of eight animals. Distilled water is in Group I (negative control).Group II Mitoxantrone was delivered intraperitoneally with a dosage of 2.50 mg/ kg in order to achieve a cumulative complete dosage of 7.50 mg /kg by day 20. Group III Zinc gluconate was orally provided at a dosage of 20 mg/ kg/day, and Mitoxantrone was injected intraperitoneally at a rate of 2.50 mg/kg. The goal was to attain a cumulative total dosage of 7.50mg/ kg by day 20.After 48 hours following the completion of the treatment period, diethyl ether was used to euthanize each animal (i.e., on day 22). Serum was used to determine the activity of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes.Each animal's liver was removed in order to perform a terminal deoxynucleotidyl-transferase-mediated-deoxyuridine-triphosphate, necked labeling (TUNEL) test to detect DNA fragmentation. Results Zinc gluconate significantly (P<0.05) decreased blood ALT and AST, and group III showed a higher percentage of normal hepatocyte cells and a lower percentage of apoptotic cells than group II. Conclusions Zinc gluconate may have a protective effect against the hepatotoxicity induced by Mitoxantrone in rats.