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The gaseous signalling molecule, hydrogen sulfide (H 2 S) has antioxidant, anti-inflammatory and anti-apoptotic properties. Since oxidative stress has been implicated in the pathogenesis of cataracts and lenticular hydrogen peroxide (H 2 O 2 ) is elevated in some cataract patients, the present study investigated the ability of H 2 S-releasing compounds to prevent H 2 O 2 -induced cataract formation in cultured bovine lenses. Lenses were cultured in either Dulbecco's Modified Eagle Medium (DMEM; control); H 2 O 2  (50 mM); ascorbic acid (AA; 3 mM) (positive control); and the H 2 S-releasing compounds (diallyl trisulfide [DATS] or GYY4137) in the presence of H 2 O 2  (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 H 2 S-releasing compounds. Both DATS (10 −7 M – 10 −4 M) and GYY4137 (10 −7 M – 10 −4 M) significantly ( p  &lt; .001) attenuated H 2 O 2  (50 mM)-induced loss in transmittance, with DATS (10 −4 M) and GYY4137 (10 −7 M) 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 (10 −5 M – 10 −4 M) and GYY4137 (10 −7 M – 10 −5 M)-treated lenses had relatively clear grids after 120 hours, compared to H 2 O 2  (50 mM)-treated lenses. The H 2 O 2  (50 mM)-induced decline in total GSH content and total SOD activity were significantly ( p  &lt; .001; n = 5) reversed by DATS (10 −4 M) and GYY4137 (10 −7 M). After 24 hours, DATS (10 −4 M) and GYY4137 (10 −7 M) significantly ( p  &lt; .001; n = 4) reduced cytotoxicity of primary bovine lens epithelial cells by 33.88 ± 4.59% and 36.19 ± 10.53%, respectively. Both H 2 S-releasing compounds protected cultured bovine lenses against oxidative stress-induced cataract formation. The slow-releasing H 2 S compound, GYY4137 was more potent than DATS in restoring lenticular total GSH content and total SOD activity along with reducing H 2 O 2  (50 mM)-induced cytotoxicity

Protective Action of Hydrogen Sulfide-Releasing Compounds against Oxidative Stress-Induced Cataract Formation in Cultured Bovine Lenses