Regulation of Cataractogenesis in Culture Bovine Lenses by 5-Phenyldithiole-3-Thione-NSAID Hybrid Molecules
type: CreativeWork
description: Although cataract is one of the leading causes of blindness worldwide, there is no pharmacological management for the disease. There is evidence that L-cysteine, a substrate for the endogenous production of hydrogen sulfide (H2S) and Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can mitigate cataractogenesis. Therefore, this study investigated the pharmacological actions and mechanisms by which ATB 343 (indomethacin & H2S donor) and ATB 337 (diclofenac & H2S donor) regulate time-dependent and hydrogen peroxide (H2O2)-induced cataractogenesis in cultured bovine lenses, ex vivo. Dulbecco's Modified Eagle's medium (DMEM)-cultured lenses exhibited a time-dependent decrease in transmittance and a corresponding loss of lens optical clarity up to 72 hours. Except for ATB 343 (10-7 mM) that increased transmittance by 26.91% (n=16; p<0.01) after 24 hours, all concentrations of ATB 343 and ATB 337 tested (10-8 M - 10-4 M) decreased transmittance in cultured bovine lenses. Moreover, neither indomethacin (10-8 M - 10-4 M), diclofenac (10-8 M - 10-4 M), nor elevation of pH attenuated time-dependent lens degradation, ex vivo. Interestingly, H2O2 accelerated lens opacification in a concentration-dependent manner, achieving a significant (p<0.001) inhibition of 45.11% (10 mM; n=24) and 42.77% (50 mM; n=12) after 72 hours. Whereas ATB 343 (10-8 M, 10-7M & 10-6 M) partially attenuated H2O2 (10 mM)-induced loss in transmittance up to 72 hours, achieving the highest magnitude of attenuation after 6 hours of 33.21% (n=6; p<0.001); 29.40% (n=6; p<0.001) and 15.20% (n=6; p<0.05), it partially attenuated H2O2 (50 mM)-induced lens opacification in cultured bovine lenses up to 24 hours by 39.30% (n=12; p<0.001), 46.11% (n=9; p<0.001) and 9.30% (n=24; p>0.05) (24 hours), respectively. Similarly, ATB 337 (10-8M to 10-6M) partially reversed H2O2 (10 mM and 50 mM)-induced degradation up to 72 hours. After 48 hours, ATB 343 and ATB 337 (10-7M) significantly (n=3; p<0.05) enhance…
abstract: Although cataract is one of the leading causes of blindness worldwide, there is no pharmacological management for the disease. There is evidence that L-cysteine, a substrate for the endogenous production of hydrogen sulfide (H2S) and Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can mitigate cataractogenesis. Therefore, this study investigated the pharmacological actions and mechanisms by which ATB 343 (indomethacin & H2S donor) and ATB 337 (diclofenac & H2S donor) regulate time-dependent and hydrogen peroxide (H2O2)-induced cataractogenesis in cultured bovine lenses, ex vivo. Dulbecco's Modified Eagle's medium (DMEM)-cultured lenses exhibited a time-dependent decrease in transmittance and a corresponding loss of lens optical clarity up to 72 hours. Except for ATB 343 (10-7 mM) that increased transmittance by 26.91% (n=16; p<0.01) after 24 hours, all concentrations of ATB 343 and ATB 337 tested (10-8 M - 10-4 M) decreased transmittance in cultured bovine lenses. Moreover, neither indomethacin (10-8 M - 10-4 M), diclofenac (10-8 M - 10-4 M), nor elevation of pH attenuated time-dependent lens degradation, ex vivo. Interestingly, H2O2 accelerated lens opacification in a concentration-dependent manner, achieving a significant (p<0.001) inhibition of 45.11% (10 mM; n=24) and 42.77% (50 mM; n=12) after 72 hours. Whereas ATB 343 (10-8 M, 10-7M & 10-6 M) partially attenuated H2O2 (10 mM)-induced loss in transmittance up to 72 hours, achieving the highest magnitude of attenuation after 6 hours of 33.21% (n=6; p<0.001); 29.40% (n=6; p<0.001) and 15.20% (n=6; p<0.05), it partially attenuated H2O2 (50 mM)-induced lens opacification in cultured bovine lenses up to 24 hours by 39.30% (n=12; p<0.001), 46.11% (n=9; p<0.001) and 9.30% (n=24; p>0.05) (24 hours), respectively. Similarly, ATB 337 (10-8M to 10-6M) partially reversed H2O2 (10 mM and 50 mM)-induced degradation up to 72 hours. After 48 hours, ATB 343 and ATB 337 (10-7M) significantly (n=3; p<0.05) enhance…
author: Leonce Ngaelle, Maffofou Nkenyi
language: en_US
date published: 2020-09-21
date modified: 2026-07-24T01:51:08Z
provider: Creighton University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Creighton University

PropertyValue
property ID: Handle
value: http://hdl.handle.net/10504/128560