Beneficial effects of ascorbic acid on ivermectin repeated high-dose therapy in rabbits: biochemical and histopathological investigations

Ivermectin (IVM) is a lipophilic anthelmintic drug widely used for the control of internal and external parasites in both human and veterinary medicine. Conversely, overdoses of IVM are associated with resistance and efficacy problems. The present study aimed to evaluate the effects of repeated administration of a high dose of IVM alone or with combination of ascorbic acid (AA) in male young rabbits (Oryctolagus cuniculus) via biochemical and histological investigations. Twenty rabbits were divided into four groups (n=5) and treated for three consecutive weeks: Control group; IVM group (2 mg/kg of body weight subcutaneously, 3 times a week); IVM + AAg (20 mg/mL) group and IVM + AAf (200 mg/kg of diet) group. IVM induced a disruption of hepatic biochemical parameters and lipid profile with a statistically significant (p < 0.05) increase in glucose, ALT, AST, GGT, HDL-C and a significant decrease of TC, TG, LDL-C, VLDL-C in IVM group compared to control group. Co-administration of AA moderately improved those biochemical parameters. Histopathological changes following IVM treatment in liver comprised loss of normal hepatocytes structure, central vein dilation and portal vein congestion. The lung showed abnormal structure of intrapulmonary bronchus, dilated bronchioles and alveoli and congested pulmonary artery. Nevertheless, the AA treatment groups revealed significant improvement when co-administered orally with IVM. This study suggested that AA has a beneficial ameliorative role against toxic effects induced by repeated high-dose of IVM