N-acetylcysteine amide protects against dexamethasone-induced cataract related changes in cultured rat lenses - Advances in Biological Chemistry

ABC > Vol.4 No.1, February 2014

N-acetylcysteine amide protects against dexamethasone-induced cataract related changes in cultured rat lenses ()

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DOI: 10.4236/abc.2014.41005 3,864 Downloads 6,802 Views Citations

Author(s)

Shakila Tobwala, Eylem Y. Pinarci, Yasaswi Maddirala, Nuran Ercal

Affiliation(s)

Department of Chemistry, Missouri University of Science and Technology, Rolla, USA.
Department of Ophthalmology, Baskent University, Istanbul, Turkey.

ABSTRACT

Glucocorticoids (GCs) are one of the most widely used immunosuppressive and anti-inflammatory agents. However, their long term and systemic use is associated with adverse drug reactions including posterior subcapsular cataracts as one of its ocular complications. Balanced redox state is crucial for maintenance of lens transparency, and a high content of glutathione (GSH) in the lens is believed to play a key role in doing so. Depletion of GSH is implicated in the etiopathogenesis of dexamethasone-induced cataracts and, therefore, the present study was sought to evaluate the efficacy of a novel thiol antioxidant, N-acetylcysteine amide (NACA), in preventing dexamethasone-induced cataractogenesis. Cataract formation was induced by incubation of rat lenses with 5 μM dexamethasone. To assess whether NACA had a significant impact on dexamethasone-induced cataracts, the rat lenses were divided into four groups: 1) control group (Dulbecco’s Modified Eagle Medium (DMEM), 2) dexamethasone group (DMEM with 5 μM dexamethasone), 3) NACA-only group (50 μM NACA solution), and 4) NACA pretreatment group (50 μM NACA for 6 hours followed by 5 μM dexamethasone only for 18 hours). Lenses were cultured for 7 days at 37°C under 5% CO₂. Lenses were evaluated daily using a dissecting microscope and photographed and graded for the development of opacity. The rat lenses in both the control and the NACA-only groups were clear, whereas all lenses within the dexamethasone-only group developed well-defined cataracts. Overall observations indicated that NACA inhibits cataract formation by limiting lipid peroxidation and increasing the ratio of GSH/GSSG in lens. Therefore, NACA can be developed into a potential adjunctive therapeutic option for patients undergoing therapy with GCs to inhibit glucocorticoid-induced cataracts.

KEYWORDS

Dexamethasone; Cataracts; Oxidative Stress; Antioxidant; N-Acetylcysteine Amide

Share and Cite:

Tobwala, S. , Pinarci, E. , Maddirala, Y. and Ercal, N. (2014) N-acetylcysteine amide protects against dexamethasone-induced cataract related changes in cultured rat lenses. Advances in Biological Chemistry, 4, 26-34. doi: 10.4236/abc.2014.41005.

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