Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
Published: October 2024
AI Article Synopsis
Article Abstract
We have evidence that hydrogen sulfide (HS)-releasing compounds can reduce intraocular pressure in normotensive and glaucomatous rabbits by increasing the aqueous humor (AH) outflow through the trabecular meshwork. Since HS has been reported to possess neuroprotective actions, the prevention of retinal ganglion cell loss is an important strategy in the pharmacotherapy of glaucoma. Consequently, the present study aimed to investigate the neuroprotective actions of HS-releasing compounds against hydrogen peroxide (HO)-induced oxidative stress in an isolated bovine retina. The isolated neural retinae were pretreated with a substrate for HS biosynthesis called L-cysteine, with the fast HS-releasing compound sodium hydrosulfide, and with a mitochondrial-targeting HS-releasing compound, AP123, for thirty minutes before a 30-min oxidative insult with HO (100 µM). Lipid peroxidation was assessed via an enzyme immunoassay by measuring the stable oxidative stress marker, 8-epi PGF2α (8-isoprostane), levels in the retinal tissues. To determine the role of endogenous HS, studies were performed using the following biosynthesis enzyme inhibitors: aminooxyacetic acid (AOAA, 30 µM); a cystathione-β-synthase/cystathionine-γ-lyase (CBS/CSE) inhibitor, α-ketobutyric acid (KBA, 1 mM); and a 3-mercaptopyruvate-s-sulfurtransferase (3-MST) inhibitor, in the absence and presence of HS-releasing compounds. Exposure of the isolated retinas to HO produced a time-dependent (10-40 min) and concentration-dependent (30-300 µM) increase in the 8-isoprostane levels when compared to the untreated tissues. L-cysteine (10 nM-1 µM) and NaHS (30 -100 µM) significantly ( < 0.001; n = 12) prevented HO-induced oxidative damage in a concentration-dependent manner. Furthermore, AP123 (100 nM-1 µM) attenuated oxidative HO damage resulted in an approximated 60% reduction in 8-isoprostane levels compared to the tissues treated with HO alone. While AOAA (30 µM) and KBA (1 mM) did not affect the L-cysteine evoked attenuation of HO-induced oxidative stress, KBA reversed the antioxidant responses caused by AP123. In conclusion, various forms of HS-releasing compounds and the substrate, L-cysteine, can prevent HO-induced lipid peroxidation in an isolated bovine retina.
Introduction: Cerebral malaria (CM) is a potentially fatal cerebrovascular disease of complex pathogenesis caused by Plasmodium falciparum. Hydrogen sulfide (HS) is a physiological gas, similar to nitric oxide and carbon monoxide, involved in cellular metabolism, vascular tension, inflammation, and cell death. HS treatment has shown promising results as a therapy for cardio- and neuro- pathology.
