Abstract
BackgroundThe present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups.MethodsForty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins.ResultsMorphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite- injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA.ConclusionsThe data suggest that NACA has the potential to significantly improve vision and decrease the burden of cataract-related loss of function. Prevention and reversal of cataract formation could have a global impact. Development of pharmacological agents like NACA may eventually prevent cataract formation in high-risk populations and may prevent progression of early-stage cataracts. This brings a paradigm shift from expensive surgical treatment of cataracts to relatively inexpensive prevention of vision loss.
Highlights
The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups
Our results demonstrate that NACA administration bolstered antioxidant defenses of selenite-dosed animals by replenishing GSH, inhibiting lipid peroxidation, preventing accumulation of calcium, thereby preventing activation of m-calpain and eventually preserving the lens crystallin proteins
Effects of Na2SeO3 and NACA on cataract formation in the lens Intraperitoneal injection of Na2SeO3 (19 μmol/kg) on postpartum day 10 was sufficient to induce cataract formation, which was visible by the time the rat pups opened their eyes
Summary
The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups. Cataract is a progressive loss of transparency of the lens that affects vision It is the most common cause of curable blindness, accounting for more than 50% of cases worldwide [1]. Oxidative stress implies an imbalance between the rate of oxidant production and the rate of detoxification, with the rate of production being significantly higher compared to that of detoxification by antioxidants [10] An organism counteracts this condition with its natural antioxidant defense systems, but with age, oxidants accumulate while antioxidant defenses gradually diminish, which is likely the most important mechanism in age-related cataract formation. N-acetylcysteine (NAC), a glutathione (GSH) prodrug, has previously been tried in selenite-induced cataracts in vivo [25] and was shown to prevent oxidative damage to the lens, slowing down cataractogenesis
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