TITLE:
N-acetylcysteine amide protects against dexamethasone-induced cataract related changes in cultured rat lenses
AUTHORS:
Shakila Tobwala, Eylem Y. Pinarci, Yasaswi Maddirala, Nuran Ercal
KEYWORDS:
Dexamethasone; Cataracts; Oxidative Stress; Antioxidant; N-Acetylcysteine Amide
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.4 No.1,
February
10,
2014
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.