Cataracts, one of the leading causes of preventable blindness worldwide, refers to lens degradation that is characterized by clouding, with consequent blurry vision. As life expectancies improve, the number of people affected with cataracts is predicted to increase worldwide, especially in low-income nations with limited access to surgery. Although cataract surgery is considered safe, it is associated with some complications such as retinal detachment, warranting a search for cheap, pharmacological alternatives to the management of this ocular disease. The lens is richly endowed with a complex system of non-enzymatic and enzymatic antioxidants which scavenge reactive oxygen species to preserve lens proteins. Depletion and/or failure in this primary antioxidant defense system contributes to the damage observed in lenticular molecules and their repair mechanisms, ultimately causing cataracts. Several attempts have been made to counteract experimentally induced cataract using in vitro, ex vivo, and in vivo techniques. The majority of the anti-cataract compounds tested, including plant extracts and naturally-occurring compounds, lies in their antioxidant and/or free radical scavenging and/or anti-inflammatory propensity. In addition to providing an overview of the pathophysiology of cataracts, this review focuses on the role of various categories of natural and synthetic compounds on experimentally-induced cataracts.
Hydrogen sulfide (HS) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in physiological and pathological processes in the eye has led to several in vitro, ex vivo, and in vivo studies to understand its pharmacological role in some mammalian species. Evidence from literature demonstrates that 4 enzymes responsible for the biosynthesis of this gas (cystathionine β-synthase, CBS; cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea, iris, ciliary body, lens, and retina. Studies of the pharmacological actions of HS (using several compounds as fast- and slow-releasing gas donors) on anterior uveal tissues reveal an effect on sympathetic neurotransmission and the ability of the gas to relax precontracted iris and ocular vascular smooth muscles, responses that were blocked by inhibitors of CSE, CBS, and K channels. In the retina, there is evidence that HS can inhibit excitatory amino acid neurotransmission and can also protect this tissue from a wide variety of insults. Furthermore, exogenous application of HS-releasing compounds was reported to increase aqueous humor outflow facility in an ex vivo model of the porcine ocular anterior segment and lowered intraocular pressure (IOP) in both normotensive and glaucomatous rabbits. Taken together, the finding that HS-releasing compounds can lower IOP and can serve a neuroprotective role in the retina suggests that HS prodrugs could be used as tools or therapeutic agents in diseases such as glaucoma.
Cataracts, one of the leading causes of preventable blindness worldwide, refers to lens degradation that is characterized by clouding, with consequent blurry vision. As life expectancies www.videleaf.com antioxidant and/or free radical scavenging and/or antiinflammatory propensity. In addition to providing an overview of the pathophysiology of cataracts, this review focuses on the role of various categories of natural and synthetic compounds on experimentally-induced cataracts.
Both natural and synthetic compounds that release hydrogen sulfide (H2S) such as diallyl trisulfide and naproxen‐H2S hybrids growth and proliferation of human colon HT29 cells (Lai et al. J. Cell. Mol. Med 19: 474, 2014; Kodela et al. Drug Des. Dev. Ther. 9:4873, 2015). Aims of the present study were: (a) to investigate the pharmacological action of L‐cysteine (substrate for the biosynthesis of H2S) and NaHS (H2S‐releasing compound) on proliferation of HT29 cells at different time‐points, and (b) to study the role of enzymes (cystathionine β‐synthase, CBS and cystathionine γ‐lyase, CSE) and K+‐ATP channels on the response elicited by H2S‐producing compounds in HT29 cells. The colon adenoma HT29 cells were treated with different concentrations of L‐cysteine (1 μM – 1 mM) and NaHS (1 μM – 1 mM) for 24 and 48 hours, in the absence and presence of inhibitors of CBS and CSE, amino‐oxyacetic acid (AOA, 1 mM), an inhibitor of K+‐ATP channels, glibenclamide (GLB, 10 μM). After incubation, the anti‐proliferative response on cells caused by various agents was determined by MTT Assay. At equimolar concentrations (10 μM and 1 mM), both L‐cysteine and NaHS caused concentration‐dependent inhibitions of cell proliferation after incubation for 24 h, but increased cell growth at these same concentrations after 48 h of incubation. For instance, at 10 μM, both L‐cysteine and NaHS increased cell proliferation by 37% and 51% after 48 h of incubation. Pretreatment of cells with AOA (1 mM) had no significant (P>0.05) effect on the inhibitory response caused by L‐cysteine and NaHS after 24 h incubation. Interestingly, AOA blocked and even reversed the increase in proliferation caused by L‐cysteine (10 μM and 1 mM) and NaHS (10 μM and 1 mM) after 48 h incubation. After 24 h, both L‐cysteine and NaHS caused additional inhibitory effects on cell proliferation in HT 29 cells pretreated with GLB (10 μM). GLB blocked and even reversed the increase in proliferation caused by L‐cysteine and NaHS in HT29 cells after 48 h incubation. We conclude that H2S‐releasing compounds can elicit a time‐dependent inhibitory or excitatory action on the proliferation of HT29 cells. The inhibitory/excitatory effects caused by these compounds depends, at least in part, on endogenous biosynthesis of new gas and the activity of K+‐ATP channels in HT29 cells. Support or Funding Information This research is supported by Tittle III under the Award Number P031B090216;Title III, Part B, Historically Black Graduate Institutions (HBGI) (CFDA No. 84.031B).
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