Original ContributionCannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy
Section snippets
Materials
CBD was obtained from Tocris Bioscience (Ellisville, MO, USA). Reactive oxygen species (ROS) detection kit was purchased from Enzo Life Sciences (Plymouth Meeting, PA, USA). ATP determination kit was from Molecular Probes (Eugene, OR, USA). Antibodies against phospho-c-Jun N-terminal kinase (pJNK), JNK, microtubule-associated protein 1A/1B light-chain 3 (LC3), pP38 mitogen-activated protein kinase (MAPK), and P38 MAPK were obtained from Cell Signaling (Danvers). Antibody against CYP2E1 was a
CBD decreases ethanol-induced liver injury
To assess the effect of CBD on ethanol-induced hepatotoxicity, we induced liver injury by treating mice with ethanol (30% v/v in saline, 4 g/kg, every 12 h for 5 days). CBD (5 mg/kg, every 12 h) or vehicle was injected ip 30 min before ethanol gavage. Ethanol gavage led to an increase in serum aspartate aminotransferase (AST) that was prevented by CBD (Fig. 1A). Ethanol gavage produced a 60% decrease in hepatic ATP levels (Fig. 1C), suggestive of hepatic bioenergetic injury. This decline in ATP was
Discussion
Acute alcohol drinking induces liver steatosis [2], [19], [27], [29]. The induction of liver steatosis is promoted by CYP2E1, as wild-type mice with CYP2E1 expression displayed steatosis, but CYP2E1-knockout mice exhibit strongly decreased steatosis after acute alcohol treatment [1], [2], [19]. In the current study, lipid accumulation was found in CYP2E1-expressing HepG2 cells after ethanol treatment, and liver steatosis was observed in mice treated with acute alcohol. Mechanisms by which
Acknowledgments
This work was supported by Grants AA-018790 and AA-021362 from the NIAAA (to A.I.C.) and NIH Grant DA 008863 (to L.A.D.).
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