Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. <b>Purpose:</b> The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycer...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/1/117 |
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| Summary: | Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. <b>Purpose:</b> The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (H<sub>2</sub>S) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. <b>Methods:</b> Isolated neural retinas from cows were exposed to oxidative damage using H<sub>2</sub>O<sub>2</sub> (100 µM) for 10 min. When used, tissues were pretreated with methanandamide (1 nM–100 nM) and 2-AG (1–10 µM) for 30 min before a 10 min treatment with H<sub>2</sub>O<sub>2</sub> (100 µM). In some experiments, retinas were pretreated with inhibitors of the biosynthesis of H<sub>2</sub>S [cystathionine β-synthase/cystathionine γ-lyase (CBS/CSE), aminooxyacetic acid, AOAA 30 µM, or 3-mercaptopyruvate sulfurtransferase (3MST), α-keto-butyric acid, KBA 1 mM] and the CB1-receptor antagonist, AM251 (100 nM) for 30 min before treatment with methanandamide (1 nM–100 µM). Enzyme immunoassay measurement of 8-epi PGF2α (8-isoprostane) levels was performed to assess lipid peroxidation in retinal tissues. <b>Results:</b> In the presence of H<sub>2</sub>O<sub>2</sub> (100 µM), methanandamide (1 nM–100 µM) and 2-AG (1–10 µM) significantly (<i>p</i> < 0.001) blocked the H<sub>2</sub>O<sub>2</sub>-induced elevation in 8-isoprostane levels in the isolated bovine retina. In the presence of the CB1 antagonist AM251 (100 nM), the effect of methanandamide (1 nM) on the H<sub>2</sub>O<sub>2</sub>-induced 8-isoprostane production was significantly (<i>p</i> < 0.001) attenuated. While AOAA (30 µM) had no significant (<i>p</i> > 0.05) effect on the inhibition of H<sub>2</sub>O<sub>2</sub>-induced oxidative stress elicited by methanandamide, KBA (1 mM) reversed the neuroprotective action of methanandamide. <b>Conclusions:</b> The cannabinoids, methanandamide and 2-AG can prevent H<sub>2</sub>O<sub>2</sub>-induced oxidative stress in the isolated bovine retina. The neuroprotective actions of cannabinoids are partially dependent upon the activation of the CB1 receptors and endogenous production of H<sub>2</sub>S via the 3-MST/CAT pathway. |
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| ISSN: | 1424-8247 |