Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy

Abstract

Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.

Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy

“…Modulation of autophagy was considered to be an effective approach to alleviate liver injury (26)(27)(28). In the current study we have evaluated the effect of GCM on autophagy induction and showed that GCM caused a significant induction of 19 autophagy.…”

“…It has been shown that autophagy induction can reduce alcohol-induced hepatotoxicity possibly associated with removing damaged mitochondria and accumulated lipid droplets (26)(27)(28). We next asked if autophagy was also involved in Quantitative analysis of LC3-puncta-positive cells showed that the number of cells with LC3 puncta in GCM-treated cells was significantly increased compared with the 16 untreated control (Fig 7C).…”

Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis

“…Additionally, both compounds activate and desensitize the transient receptor potential vanilloid type-1 (TRPV1) channel [9], an emerging target in obesity and related cardiometabolic risk factors [10]. Importantly, CBD inhibits weight gain in rats on high-fat diets and the development of alcohol-induced hepatosteatosis in mice [11,12], whereas THCV improves insulin sensitivity and decreases triglyceride (TG) accumulation within the livers of obese mice [13]. THCV was recently shown to reduce insulin resistance and hypertension in a small double blind placebo-controlled clinical trial in type 2 diabetes patients with dyslipidemia [14].…”

Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

“…Although CBD is considered a biologically inactive molecule (11,12), it was reported to exert cytoprotective effects in various preclinical models and was shown to be safe in patients (13). Several preclinical studies described the protective effect of CBD in diseases associated with increased oxidative stress, inflammation and cell death such as in colitis (14), diabetic complications (15), drug-induced nephrotoxicity (16), alcohol-induced steatohepatosis (17) remodeling. Fibrotic area was quantified using ImageJ software (NIH).…”