Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats

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.

Current Trends in the Pharmacotherapy of Cataracts

“…Reversed cataract grade. Increased GSH level, thioltransferase activity, m-calpain activity, and m-calpain levels while it reduced malondialdehyde level, GSH-Px enzyme activity, and calcium levels [192] Sodium selenite Wistar rats Eye drops…”

“…Interestingly, both drugs were unable to delay progression or reverse lens opacity in the advanced stages of the disease [191], presumably due to the depletion of the total lenticular antioxidant pool. Maddirala et al (2017) also investigated the effect of both topically-and intraperitoneally-administered N-acetylcysteine amide on selenite-induced cataract formation in male Wistar rat pups [192]. In this experimental model, Na selenite (19 µM/kg body weight) was administered intraperitoneally on 10th postpartum day, intraperitoneal N-acetylcysteine amide (250 mg/kg body weight) on ninth, 11th and 13th postpartum days, while topical N-acetylcysteine drops (1%) was instilled into the eyes from postpartum 15th and 30th days.…”

“…Interestingly, both intraperitoneal and topical N-acetylcysteine amide attenuated the severity of cataracts formation, in vivo. Furthermore, the amide-treated lens homogenates exhibited higher levels of GSH content, thioltransferase and m-calpain activity, while lipid peroxidation, GSH-Rx activity, and calcium levels were reduced when compared to selenite-only treated lens homogenates [192]. Carey et al (2011) also investigated the effect of N-acetylcysteine amide on cataracts induced by the GSH synthesis inhibitor, BSO, in a Wister rat pup model of the disease.…”

Age‐dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation—A review

“…Adapted from Reference 91 acetylcysteine, and more recently N-acetylcysteine amide, have shown to prevent cataract using animal models of cataract. [107][108][109] However, studies in humans using oral administration of nutrients and antioxidants to date have proven to be largely ineffective (reviewed in Reference 104). For example, the Age Related Eye Disease Study revealed that daily intake of antioxidant vitamins C and E and zinc, 110 and additional supplementation with lutein and zeazanthine 111 had no effects in preventing or delaying cataract.…”

Effects of Murbei Leaf Extract (Morus alba L.) on Malondialdehyde (MDA) Eye Lens in Rats (Rattus novergicus) Cataract Model

“…Hasil penelitian ini didukung oleh penelitian sebelumnya yakni terjadi peningkatan kadar MDA lensa mata dan penurunan enzim antioksidan seperti SOD, CAT, GSH-PX dan peningkatan NO, Ca 2+ , anti-OHpada lensa mata tikus (Javadzadeh et al, 2009;Zhang & Hu, 2012;Aydemir et al, 2012). Penelitian terbaru yang dilakukan oleh Maddirala et al (2017) mendukung hasil dari penelitian sebelumnya bahwa pemberian sodium selenite dapat meningkatkan kadar MDA lensa dan menurunkan kadar GSH jika dibandingkan dengan kelompok normal. Sehingga pemberian sodium selenite dapat menyebabkan terjadinya stres oksidatif pada lensa mata yang dapat diketahui salah satunya dengan peningkatan kadar MDA lensa mata tikus.…”