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Previously, we showed that Ecklonia cava polyphenol (ECP) treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS) and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1) expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.

IntroductionAlcoholic liver disease is characterized by a pathological process with progressive liver damage leading to steatosis, steatohepatitis, fibrosis and finally cirrhosis. Ethanol metabolism‐associated oxidative stress contributes to be the pathogenesis of alcoholic liver disease. Here, we examined the effect of the extract of Ecklonia cava, brown algae, on ethanol‐induced liver injury in rat primary hepatocytes.MethodsIsolated hepatocytes were cultured with or without 100 mM ethanol. Ecklonia cava polyphenol (ECP) was dissolved in dimethylsulfoxide. ECP (0~25 μg/ml) was added to culture medium with ethanol simultaneously. The cells were cultured for 0~24 hrs.ResultsIn the cultured hepatocytes, ECP treatment suppressed the ethanol‐induced increase in cell death by inhibiting cytochrome p450 2E1(CYP2E1) expression and activity, which is related to the production of reactive oxygen species (ROS) when large quantities of ethanol are oxidized. On the other hand, ECP treatment increased the activity of alcohol dehydrogenase.ConclusionThese results suggest that ECP protects against ethanol‐induced liver injury via regulating alcoholic metabolizing enzymes and then suppressing ROS production.

IntroductionYerba–Mate is popular tea beverage produced and consumed in South America. Ethanol metabolism‐associated oxidative stress contributes to the pathogenesis of alcoholic liver disease. The objective of this study was to reveal the protective effect of a Yerba–Mate tea extract on ethanol‐induced liver injury.MethodsIsolated hepatocytes were cultured with or without 100 mM ethanol. An extract of Yerba‐Mate tea (EMT) was added to the culture medium with ethanol simultaneously. Male Wistar rats were fed a diet with or without 0.005% or 0.02% EMT. Animals were given drinking water containing ethanol 5% (v/v) together with two doses of CCl4 (0.1 ml/kg BW, i.p.) weekly for 3 weeks.ResultsIn the cultured hepatocytes, EMT treatment suppressed the ethanol‐induced increase in cell death by inhibiting cytochrome p450 2E1 (CYP2E1) activity, which is related to the production of reactive oxygen species. We examined the effects of EMT on serum ALT activity and the progression of liver fibrosis in rats treated with ethanol and CCl4. EMT treatment suppressed plasma ALT activity in the ethanol‐ and CCl4‐treated rats. Furthermore, EMT treatment decreased CYP2E1 expression and increased ADH expression in the ethanol‐ and CCl4‐treated rats. EMT treatment protected the rats against ethanol‐ and CCl4‐induced liver injury.ConclusionEMT may be a candidate for preventing ethanol‐induced liver injury.