Attenuation of 4-hydroxynonenal-induced cataractogenesis in rat lens by butylated hydroxytoluene.
OBJECTIVE
We have previously shown that 4-hydroxynonenal (4-HNE) causes opacification of cultured rat lenses and that a novel group of glutathione S-transferases (GSTs) exhibit high specific activity towards 4-HNE. Previous studies have shown that t-butylated hydroxy toluene (BHT) induced GSTs in cultured rat lens. Therefore, the purpose of the present studies was to investigate if the opacification of rat lenses exposed to 4-HNE is ameliorated by pre-culturing the lenses in media containing BHT.


METHODS
Rat lenses were divided into four groups. Group I and II were controls and groups III and IV were cultured in the presence of 100 microM 4-HNE. Groups II and IV were pre-cultured in the media containing 10 microM BHT for 24 hrs which was designated as 0 time point. Lenses were withdrawn at 24 and 72 h and evaluated for opacification by digital image analysis. Induction of the specific GST isozyme (gammaGST8-8) was studied in the lens epithelium by immunohistochemical studies. Results. Digital image analysis revealed amelioration in opacification induced by 4-HNE, when the lenses were precultured with BHT. Immunohistochemical studies show that BHT induced GST8-8 several folds in the epithelium.


CONCLUSIONS
These studies indicate that pretreatment with BHT would increase the lens capacity to detoxify 4-HNE by conjugating it with GSH, thus assigning an important detoxication role to this specific GST isozyme in oxidative cataract.
Srivastata
S K
SK
Department of Human Biological Chemistry, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
Awasthi
S
S
Wang
L
L
Bhatnagar
A
A
Awasthi
Y C
YC
Ansari
N H
NH
D000447:Aldehydes / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008658:Inactivation, Metabolic; D007527:Isoenzymes / Q000096:biosynthesis; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D000447:Aldehydes; D000975:Antioxidants; D007527:Isoenzymes; D002084:Butylated Hydroxytoluene; D005982:Glutathione Transferase; C027576:4-hydroxy-2-nonenal