Pseudocannabinoid H4CBD Reduces Cardiac Damage Indicator 4HNE in OLETF (Otsuka Long Evans Tokushima Fatty) Rats

Abstract

Cardiovascular disease (CVD) is a leading cause of death globally and MetS is an associated precursor of CVD. Of the 6 known cluster factor conditions of MetS, obesity, and poor glucose tolerance are known to contribute to high lipid peroxidation, which can contribute to the generation of damaging free radical species and a pro-oxidant system. Cannabidiol (CBD) is a known antioxidant and a growing understanding of CBD analogs and pseudocannabinoids, like H4CBD, implicate similar antioxidant effects. However, little is known about the effects of CBD analogs on MetS-associated cardiac tissue damage. To better understand these effects during extreme metabolic dysfunction, 41-weeks-old animals were assigned into three groups, (n=8/group): (1) one-lean-strain control, Long Evans Tokushima Otsuka (LETO), (2) untreated OLETF, and (3) OLETF + H4CBD (200 mg/kg/day x 4 weeks). Our hypothesis focuses on the prospect that ongoing treatment with H4CBD in a MetS model using Otsuka Long-Evans Tokushima Fatty (OLETF) rats will reduce indicators of lipid peroxidation including 4-hydroxynonenal (4HNE), a toxic end product of lipid peroxidation. After the 4-week treatment, cardiac tissue was analyzed for 4-hydroxynonenal (4HNE) protein expression. We found that H4CBD decreased cardiac 4HNE protein expression in treated OLETF rats by 68% (p<0.05) compared to OLETF control, which indicates H4CBD attenuated cardiac lipid peroxidation overall. Although the 4-week treatment of H4CBD was not suffcient to ameliorate MetS-associated hypertension, the reduction of 4HNE suggests that the attenuation of cardiac damage is independent of arterial pressure. These data indicate that H4CBD and its derivatives hold promise for therapeutic use in managing CVD and related metabolic syndrome-associated pathologies. Undergraduate Research Training Initiative for Student Enhancement (U-RISE), Center for Medical Cannabis Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.