title: In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide.
abstract: The effects of N-acetylcysteine amide (NACA), a free radical scavenger, on cataract development were evaluated in Wistar rat pups. Cataract formation was induced in these animals with an intraperitoneal injection of a glutathione (GSH) synthesis inhibitor, l-buthionine-(S,R)-sulfoximine (BSO). To assess whether NACA has a significant impact on BSO-induced cataracts, the rats were divided into four groups: (1) control, (2) BSO only, (3) NACA only, and (4) NACA+BSO. The control group received only saline ip injections on postpartum day 3, the BSO-only group was given ip injections of BSO (4mmol/kg body wt), the NACA-only group received ip injections of only NACA (250mg/kg body wt), and the NACA+BSO group was given a dose of NACA 30min before administration of the BSO injection. The pups were sacrificed on postpartum day 15, after examination under a slit-lamp microscope. Their lenses were analyzed for selective oxidative stress parameters, including glutathione (reduced and oxidized), protein carbonyls, catalase, glutathione peroxidase, glutathione reductase, and malondialdehyde. The lenses of pups in both the control and the NACA-only groups were clear, whereas all pups within the BSO-only group developed well-defined cataracts. It was found that supplemental NACA injections during BSO treatment prevented cataract formation in most of the rat pups in the NACA+BSO group. Only 20% of these pups developed cataracts, and the rest retained clear lenses. Further, GSH levels were significantly decreased in the BSO-only treated group, but rats that received NACA injections during BSO treatment had these levels of GSH replenished. Our findings indicate that NACA inhibits cataract formation by limiting protein carbonylation, lipid peroxidation, and redox system components, as well as replenishing antioxidant enzymes.
authors.affiliation: Department of Chemistry, Missouri University of Science & Technology, Rolla, MO 65409, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Carey
authors.forename: Eylem Y
authors.initials: EY
authors.lastname: Pinarci
authors.forename: Suman
authors.initials: S
authors.lastname: Penugonda
authors.forename: Humeyra
authors.initials: H
authors.lastname: Karacal
authors.forename: Nuran
authors.initials: N
authors.lastname: Ercal
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002374:Catalase / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; C487056:N-Acetylcysteinamide; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D000111:Acetylcysteine