Potential Protective Effects of NSAIDs/ASA in Oxidatively Stressed Human Lens Epithelial Cells and Intact Mouse Lenses in Culture

Abstract

Purpose: To study possible toxic effects of indomethacin, diclofenac, and celecoxib (NSAIDs) and acetylsalicylic acid (ASA) as well as potentially protective effects of these substances in oxidatively stressed human lens epithelial cells (HLEC) and in intact mouse lenses in culture. Methods: HLEC and mouse lenses were incubated with NSAIDs or ASA alone or in the presence of H₂O₂. To study apoptosis the cells were then either stained with Hoechst 33342 or assayed for caspase-3 activity. Mouse lenses were studied with respect to lens transparency. Results: Low concentrations of NSAIDs/ASA caused a significant protection against H₂O₂-induced apoptosis in HLEC whereas higher concentrations were toxic. Conclusion: The protective effects of NSAIDs/ASA against oxidative damage are confined to a relatively small therapeutic window.

Intracellular Effects of NSAIDs/ASA in Oxidatively Stressed Human Lens Epithelial Cells in Culture

“…It is considered that H 2 O 2 , a major oxidant, contributes to cataract formation [22] . In a previous study, we found that low concentrations of the nonselective COX-1 and COX-2 inhibitors indomethacin and diclofenac, the selective COX-2 inhibitor celecoxib and ASA protected against hydrogen peroxide-induced apoptosis in human lens epithelial cells (HLECs) [23] . Higher concentrations of NSAIDs ( 1 0.5 M ) or ASA ( 1 30 m M ) induced apoptosis in itself, which further emphasizes that both protective and toxic effects of NSAIDs/ASA can be seen depending on the concentration used.…”

Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

“…Many stimuli that cause oxidative stress are sufficient to induce apoptosis through the mitochondrial pathway. Previous studies have demonstrated that caspase-3 plays a key role in the HLE cell apoptosis induced by oxidative stress [10,[12][13][14], suggesting a mitochondria-mediated signaling pathway is involved. In addition, in vitro studies have identified caspase-9, Apaf1 and cytochrome c as participants in a complex important for caspase-3 activation [25], and there is reduced apoptosis in caspase-9 deficient mice [26].…”

“…Elevated levels of H 2 O 2 are reported in the aqueous humor of cataract patients [8], and both internal and external sources of oxidative stress induce LEC apoptosis and cause lens opacification in vitro [9][10][11]. Although the detail signaling pathways involved are still unclear, caspase-3 has been shown to play a key role in the lens epithelial cell apoptosis induced by oxidative stress [10,[12][13][14]. In addition, a previous study Parthenolide inhibits lens cell apoptosis 566 npg has suggested that aB-crystallin, a molecular chaperon, can prevent LEC from apoptosis through inhibition of activation of caspase-3 [10].…”

“…Although the detail signaling pathways involved are still unclear, caspase-3 has been shown to play a key role in the lens epithelial cell apoptosis induced by oxidative stress [10,[12][13][14]. In addition, a previous study Parthenolide inhibits lens cell apoptosis 566 npg has suggested that aB-crystallin, a molecular chaperon, can prevent LEC from apoptosis through inhibition of activation of caspase-3 [10]. However, until now there have been no effective clinical methods for preventing the LEC apoptosis induced by oxidative stress.…”

An Experimental Study to Evaluate Protective Effects of Naproxen and Valdecoxib on Naphthalene Induced Cataract in Albino Rats

“…19,21 The concentration of glutathione, a tripeptide thiol decreases with age in the lens and more markedly in cataracts. 22,24 An approach to glutathione level inside the lens by its increased synthesis or decreased breakdown was tried by some groups using agents acting against glutathione. The potential role of vitamins and antioxidants in preventing various diseases is well documented.…”