Glutathione isopropyl ester (YM737) inhibits the progression of X-ray-induced cataract in rats.
The effect of glutathione (GSH) isopropyl ester on the progression of X-ray-induced cataract was investigated in rats. Intraperitoneal administration of 20 mg/kg GSH isopropyl ester, three times weekly, 1 day after a single irradiation dose delayed the progression of X-ray-induced cataracts significantly. The amount of non-protein SH groups and the Na+/K+ ratio in the lenses of drug-treated rats were maintained at the normal levels even 27 weeks after irradiation. Posttreatment with the drug resulted in a significantly lower level of malondialdehyde in the irradiated lenses than in the nontreated lenses. When 500 mg/kg GSH-isopropyl ester was administered by i.p. injection to normal rats, the GSH-ester was detected in plasma and aqueous humor after 15 min. In the lenses of the GSH-isopropyl ester-injected rats, the GSH level was 120% of that in the non-treated rats after 4 h, suggesting that GSH-isopropyl ester is transported from the aqueous humor to the lens and there converted to GSH after about 4 h. Our observations lead us to conclude that the delay of X-ray-induced lens opacity progression is due to maintenance of normal lenticular GSH levels achieved by post-irradiation administration of GSH-isopropyl ester. However, continuous administration of 100 mg/kg after irradiation had no effect on the progression of cataracts induced by X-rays.
Kobayashi
S
S
Kyoritsu College of Pharmacy, Tokyo, Japan.
Kasuya
M
M
Shimizu
K
K
Ishii
Y
Y
Takehana
M
M
Sakai
K
K
Suzuki
N
N
Itoi
M
M
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002386:Cataract / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D008315:Malondialdehyde / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014965:X-Rays
D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; C058293:glutathione monoisopropyl ester; D012964:Sodium; D005978:Glutathione; D011188:Potassium