Evaluation of the Protective effect of AMPA/Kainate Receptor Antagonist on Ethambutol Induced Retinal Toxicity Using ERG in Rats

Abstract

Purpose: : To study the protective effect of non-NMDA antagonist trimetazidine against ethambutol induced retinal toxicity in rats using Electroretinogram (ERG).

Methods: : White albino rats of either sex weighing 250-300gms (n=6) were randomized into three groups: Group 1 received distill water and served as a vehicle control. Group 2 received oral ethambutol at the dose of 200mg/kg/day and served as control. Group 3 fed with oral ethambutol and injected with trimetazidine intraperitonially at the dose of 3mg/kg/day. All treatments were continued for 21 days and ERG was recorded on 0, 1, 7, 14th and 21st day after the initiation of experiment. ERG with gold electrodes (with green and white light) were recorded after anesthesia using a standard procedure. Vitreous humor and blood samples were subjected quantification of ethambutol using liquid chromatography coupled tandem mass spectroscopy.

Results: : Ethambutol induced ERG changes were observed from 7th day following the initiation of treatment in rats. Differences in ERG were observed between white and green light conditions suggesting the ethambutol toxicity on photoreceptors. Trimetazidine pretreatment significantly reversed ERG changes induced by ethambutol (as observed in both white (P=0.002) and green (P=0.004) light records for "a" wave amplitude). Interestingly, trimetazidine pretreatment significantly reversed "b" wave amplitude recorded in green light (P=0.007) whereas this effect was insignificant on white light condition.

Conclusions: : Trimetazidine showed a significant reversal of ethambutol induced ERG changes in rats. This effect of trimetazidine was prominent in the ERG observed with green light as compared white light. This study indicates the possible beneficial role of trimetazidine in reversal of ethambutol-induced retinal toxicity.

Keywords: electrophysiology: non-clinical • color vision • retina