ATTENUATION OF 4-HYDROXYNONENAL-INDUCED CATARACTOGENESIS IN RAT LENS BY BUTYLATED HYDROXYTOLUENE

Purpose. We have previously shown that 4-hydroxynonenal (4-HNE) causes opacification of cultured rat lenses and that a novel group of glutat hione S-transferases (GSTs) exhibit high specific activity towards 4-H NE. Previous studies have shown that t-butylated hydroxy toluene (BHT) induced GSTs in cultured rat lens. Therefore, the purpose of the pres ent studies was to investigate if the opacification of rat lenses expo sed to 4-HNE is ameliorated by pre-culturing the lenses in media conta ining BHT. Methods. Rat lenses were divided into four groups. Groups I and II were controls and groups III and IV were cultured in the prese nce of 100 mu M 4-HNE. Groups II and IV were pre-cultured in the media containing 10 mu M BHT for 24 hrs which was designated as 0 time poin t. Lenses were withdrawn at 24 and 72 h and evaluated for opacificatio n by digital image analysis. Induction of the specific GST isozyme (ga mma GST(8-8)) was studied in the lens epithelium by immunohistochemica l studies. Results. Digital image analysis revealed amelioration in op acification induced by 4-HNE, when the lenses were precultured with BH T. Immunohistochemical studies show that BHT induced GST(8-8) several folds in the epithelium. Conclusions. These studies indicate that pret reatment with BHT would increase the lens capacity to detoxify 4F-HNE by conjugating it with GSH, thus assigning an important detoxication r ole to this specific GST isozyme in oxidative cataract.