Protective Action of Hydrogen Sulfide-Releasing Compounds against Oxidative Stress-Induced Cataract Formation in Cultured Bovine Lenses.
Curr Eye Res. 2021 Sep 2. Epub 2021 Sep 2. PMID: 34473602
PURPOSE: The gaseous signalling molecule, hydrogen sulfide (HS) has antioxidant, anti-inflammatory and anti-apoptotic properties. Since oxidative stress has been implicated in the pathogenesis of cataracts and lenticular hydrogen peroxide (HO) is elevated in some cataract patients, the present study investigated the ability of HS-releasing compounds to prevent HO-induced cataract formation in cultured bovine lenses.
METHODS: Lenses were cultured in either Dulbelcco's Modified Eagle Medium (DMEM; control); HO(50 mM); ascorbic acid (AA; 3 mM) (positive control); and the HS-releasing compounds (diallyl trisulfide [DATS] or GYY4137) in the presence of HO(50 mM). Lens opacity was determined using a plate reader to measure transmittance. Lens glutathione content (GSH), superoxide dismutase (SOD) activity and lactate dehydrogenase (LDH) cytotoxicity were assessed before and after treatment with the HS-releasing compounds.
RESULTS: Both DATS (10M - 10M) and GYY4137 (10M - 10M) significantly (p<0.001) attenuated HO(50 mM)-induced loss in transmittance, with DATS (10M) and GYY4137 (10M) achieving a maximal reversal of opacity by 56.86±0.01% (n = 6) and 8.39 ± 0.11% (n = 6) after 120 hours, respectively. These observations were corroborated by photographic evaluation, where DATS (10M - 10M) and GYY4137 (10M - 10M)-treated lenses had relatively clear grids after 120 hours, compared to HO(50 mM)-treated lenses. The HO(50 mM)-induced decline in total GSH content and total SOD activity were significantly (p<0.001; n=5) reversed by DATS (10M) and GYY4137 (10M). After 24 hours, DATS (10M) and GYY4137 (10M) significantly (p<0.001; n=4) reduced cytotoxicity of primary bovine lens epithelial cells by 33.88± 4.59% and 36.19 ± 10.53%, respectively.
CONCLUSION: Both HS-releasing compounds protected cultured bovine lenses against oxidative stress-induced cataract formation. The slow-releasing HS compound, GYY4137 was more potent than DATS in restoring lenticular total GSH content and total SOD activity along with reducing HO(50mM)-induced cytotoxicity.