Enhanced Role of Grapefruit Juice on the Antischistosomal Activity of Artemether on the Liver of Schistosoma haematobium Infected Hamsters

Abstract

Artemether (ART) is an efficacious anti-malarial drug that also displays antischistosomal properties. Laboratory studies have found that ART curtails the development of schistosoma worms and thus prevents morbidity. Grapefruit juice was found to interact with various drugs that have been metabolized by a form of Cytochrome P450, CYP3A4, thus increasing the plasma drug concentration. This work aimed to study the effect of grapefruit juice when administered before infection with Schistosoma haematobium and/or treatment with ART on its anti-schistosomal activity. Golden hamsters were infected each with 300 S. haematobium cercariae and divided into 6 groups (A – F), as follows: Infected control (A); infected received grapefruit juice before infection (B); or received grapefruit juice before infection and treated with ART (200 mg/k) at 5,6 and 7 weeks post infection (WPI) (C); or for 3 successive doses at 12 WPI (D); infected treated with ART alone (200 mg/k) at 5,6 and 7 WPI (E); infected received grapefruit juice (0.5 ml) half an hour before treatment with ART (200 mg/k) at 5,6 and 7 WPI (co-administration) (F). All groups were sacrificed 14 WPI. Some parasitological, biochemical and histopathological estimations were done. Results revealed that, the highest percent of worm reduction was observed in-group F (94.2%) compared to group C,E & D (87.3%, 77.6% & 65.9% respectively). The level of ALT, GGT, urea, thiol, albumin and alkaline phosphatase tend to normalize in accordance with the parasitological results. Neither hepatic granuloma nor prominent histopathological changes could be detected in group F. A minimal number of granulomas (1-3/animal) was observed in group E; meanwhile, the least diameter and collagen content of hepatic S. haematobium granulomas were observed in group C (125.6±5.5 & 2.4±0.572 respectively). The results of the present study demonstrated that, co-administration of grapefruit juice just before treatment with ART at 5, 6& 7 WPI enhanced its anti-schistosomal activity and improved the histopathological changes.