TY - JOUR
T1 - In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide
AU - Carey, Joshua W.
AU - Pinarci, Eylem Y.
AU - Penugonda, Suman
AU - Karacal, Humeyra
AU - Ercal, Nuran
N1 - Funding Information:
Dr. Ercal is supported by R15DA023409-01A2 from the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH). The contents of this paper are solely the responsibility of the authors and do not represent official views of the NIDA or the NIH. The authors appreciate the efforts of Barbara Harris in editing the manuscript.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - 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 (4 mmol/kg body wt), the NACA-only group received ip injections of only NACA (250 mg/kg body wt), and the NACA + BSO group was given a dose of NACA 30 min 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.
AB - 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 (4 mmol/kg body wt), the NACA-only group received ip injections of only NACA (250 mg/kg body wt), and the NACA + BSO group was given a dose of NACA 30 min 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.
KW - BSO
KW - Cataracts
KW - Free radicals
KW - GSH
KW - N-acetylcysteine amide
KW - Oxidative stress
KW - Rats
KW - lens
UR - http://www.scopus.com/inward/record.url?scp=79951682959&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2010.12.017
DO - 10.1016/j.freeradbiomed.2010.12.017
M3 - Article
C2 - 21172425
AN - SCOPUS:79951682959
SN - 0891-5849
VL - 50
SP - 722
EP - 729
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -