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<title>A novel cannabinoid 2 (CB2) receptor agonists, LEI-102 protects against alcohol-induced liver injury | NIH Research Festival</title>
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<article><div class="banner banner--gray banner--compact" style="--banner-background-image: url('/sites/default/files/media/image/2021-03/2015.jpg');--banner-background-focus: 50% 50%"><div class="banner__wrapper"><div class="banner__container"><h2 class="banner__heading">NIH Research Festival</h2><div class="banner__content"><p><strong><time datetime="2015-09-16">September 16</time> – <time datetime="2015-09-18">18, 2015</time></strong></p></div></div></div></div></article>
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<div class="section"><div data-drupal-messages-fallback class="hidden"></div></div><main role="main"><div id="main-content" tabindex="-1"></div><div class="section"><div class="content-sidebar"><div class="content-sidebar__main"><div class="content-sidebar__main-content"><div id="block-mainpagecontent-2"><article><h1>A novel cannabinoid 2 (CB2) receptor agonists, LEI-102 protects against alcohol-induced liver injury</h1><div class="schedule"><div class="schedule__label"><div class="schedule__label-text"><time datetime="2015-09-18">Friday, September 18, 2015</time>
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– Poster Session V
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</div></div><div class="schedule__content"><div class="schedule__item"><div class="schedule__time">2:00 – 3:30 p.m.</div><div class="schedule__description"><p><strong>FAES Terrace</strong></p></div><div class="schedule__description"><p><strong>NIAAA</strong></p></div><div class="schedule__description"><p><strong>PHARM-9</strong></p></div></div></div></div><h2>Authors</h2><ul><li>Y Wang</li><li>K Erdelyi</li><li>E Holovac</li><li>G Szanda</li><li>R Cinar</li><li>B Gao</li><li>G Kunos</li><li>MVD Stelt</li><li>P Pacher</li></ul><h2>Abstract</h2><p>Cannabinoid 2 receptor (CB2) is emerging as an attractive therapeutic target for various forms of tissue injury and inflammatory diseases. CB2 receptors are predominantly expressed by immune or immune-derived cells, therefore targeting these receptors is not associated with undesirable consequences of cannabinoid 1 receptor (CB1) stimulation in the CNS or cardiovascular system. We recently identified a potent and selective CB2 agonist LEI-102. Herein, we investigated the effects of LEI-102 on liver injury induced by chronic plus binge alcohol feeding, as well as in an established nephropathy model induced by cisplatin in mice. Chronic treatment with LEI-102 markedly attenuated the alcohol feeding-induced liver transaminases elevations, hepatic inflammation (mRNA expressions of TNFα, MCP1, IL1β, MIP2 and E-Selectin, and neutrophil accumulation), oxidative/nitrative stress (lipid peroxidation, 3-nitrotyrosin formation, and expression of reactive oxygen species generating enzyme NADPH oxidase NOX2 and p67phox isoforms). LEI-102 treatment also decreased the alcohol-induced increased liver triglyceride and fat droplet accumulation (measured by oil-O-Red staining). At 3 or 10 mg/kg (p.o. or i.p.) the drug dose-dependently prevented kidney inflammation, oxidative stress, histopathological injury and renal dysfunction induced by cisplatin in mice. Furthermore, LEI-102 had excellent oral bioavailability in mice reaching high concentrations in kidney and liver. Taken together, these results show that CB2 agonist LEI-102 protects against alcohol-induced liver or cisplatin-induced kidney injury by attenuating inflammation, oxidative stress and parenchymal damage. Thus, targeting CB2 may be a promising treatment in diseases of the liver and kidney that are associated with enhanced inflammation and/or oxidative stress.</p><p><strong>Scientific Focus Area</strong>: Molecular Pharmacology</p><p class="updated"><small>This page was last updated on Friday, March 26, 2021</small></p></article>
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