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: Leah Bush, Anthonia Okolie, Jenaye Robinson, Fatima Muili, Catherine A. Opere, Sunny E. Ohia, Ya Fatou Njie Mbye
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/1/117
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author Leah Bush
Anthonia Okolie
Jenaye Robinson
Fatima Muili
Catherine A. Opere
Sunny E. Ohia
Ya Fatou Njie Mbye
author_facet Leah Bush
Anthonia Okolie
Jenaye Robinson
Fatima Muili
Catherine A. Opere
Sunny E. Ohia
Ya Fatou Njie Mbye
author_sort Leah Bush
collection DOAJ
description 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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spelling doaj-art-201f5fe4b3b64412a84a04959d19a5602025-01-24T13:45:27ZengMDPI AGPharmaceuticals1424-82472025-01-0118111710.3390/ph18010117Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen SulfideLeah Bush0Anthonia Okolie1Jenaye Robinson2Fatima Muili3Catherine A. Opere4Sunny E. Ohia5Ya Fatou Njie Mbye6Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USADepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USADepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USADepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USADepartment of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE 68178, USADepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USADepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USABoth 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.https://www.mdpi.com/1424-8247/18/1/117hydrogen sulfidecannabinoidsretinaoxidative stresslipid peroxidation
spellingShingle Leah Bush
Anthonia Okolie
Jenaye Robinson
Fatima Muili
Catherine A. Opere
Sunny E. Ohia
Ya Fatou Njie Mbye
Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
Pharmaceuticals
hydrogen sulfide
cannabinoids
retina
oxidative stress
lipid peroxidation
title Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
title_full Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
title_fullStr Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
title_full_unstemmed Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
title_short Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide
title_sort neuroprotective actions of cannabinoids in the bovine isolated retina role of hydrogen sulfide
topic hydrogen sulfide
cannabinoids
retina
oxidative stress
lipid peroxidation
url https://www.mdpi.com/1424-8247/18/1/117
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