Albendazole potentiates the neurotoxic effect of ivermectin in rat

Abstract

The study was carried out to investigate whether an interaction between albendazole and ivermectin could lead to enhanced central nervous system (CNS) toxicity. Ivermectin (0.4mg/kg body weight (b.w)) and/or albendazole (15mg/kg b.w) were daily and orally administered to albino rats for 14 days. Activities of acid phosphatase (ACP), alkaline phosphatase (ALP), catalase (CAT), Na⁺-K⁺ ATPase, Ca²⁺-Mg²⁺ ATPase and malondialdehyde (MDA) level which are considered essential to correct functioning of the brain were determined. The co-administration of the two drugs significantly caused reduction (p<0.05) in the activities of brain ACP, ALP, Na⁺-K⁺ ATPase and Ca²⁺-Mg²⁺ ATPase with corresponding increase in the serum. Separate administration of ivermectin or albendazole did not show any significant changes (p>0.05) in the activity of these enzymes. These suggest that in the presence of albendazole, ivermectin is able to reach the CNS and impair its function through neurochemical changes. Also, co-administration of ivermectin and albendazole led to a significant increase (p<0.05) in brain CAT activity as well as serum and brain MDA concentrations. This may be an indication that the drugs have other mechanisms of action, such as increasing oxidative damage in the CNS. Overall, these findings suggest that both drugs exert additive effect when co-administered.

Keywords: Combination therapy, enhanced CNS toxicity, ATPases