ABSTRACT
Amiodarone, a cationic amphiphile known for its clinical efficacy as an antiarrhythmic agent, unfortunately causes serious side effects. The present study was undertaken to investigate its intestinal toxicity, on oral administration, using a Wistar rat model. The relationship of drug dose and duration on intestinal toxicity was investigated. Optimum changes were observed after 21 days of AD administration at a dose of 175 mg/Kg body wt/day and this dosage was used for further studies. Histological studies revealed decreased villi and crypt size and reduction in the cellularity of lamina propria. Marked reduction in the activities of Ca(2+)-ATPase, alkaline phosphatase, disaccharidases and Na+, K(+)-ATPase was observed. The reduction in the uptake of 14C-glucose and 14C-glycine, in vivo, was correlated to the reduction in the activities of these enzymes. The reduction in the activities of the intestinal membrane bound enzymes may be attributed to altered morphology of the villi and crypts.
