In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide

Joshua W. Carey, Eylem Y. Pinarci, Suman Penugonda, Humeyra Karacal, Nuran Ercal

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 (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.

Original languageEnglish
Pages (from-to)722-729
Number of pages8
JournalFree Radical Biology and Medicine
Volume50
Issue number6
DOIs
StatePublished - Mar 15 2011

Keywords

  • BSO
  • Cataracts
  • Free radicals
  • GSH
  • N-acetylcysteine amide
  • Oxidative stress
  • Rats
  • lens

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