Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models

Abstract

Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD.

Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders

“…These observations are noteworthy since in the literature the effects of tomato products (extract or powder) are globally more efficient to drive health effects at both epidemiological and preclinical level. This has notably been highlighted in the field of cancer , cardiovascular diseases , or hepatosteatosis . Indeed, Stice et al.…”

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…These antioxidants, contained in many fruits and vegetables, show beneficial effects on AFLD, NAFLD, and DILI, although some of these antioxidants also exhibit significant protection in other tissues such as heart, muscle, and brain (Pallauf, Giller, Huebbe, & Rimbach, 2013;Rodriguez et al, 2015). Some of these agents include inhibitors of CYP2E1 such as diallyl sulfide in garlic, phenethyl isothiocyanate (Stice et al, 2015;Yoshigae, Sridar, Kent, & Hollenberg, 2013) in crucible vegetables, or dioscin in edible plants , although these inhibitors seem less potent than the synthetic CYP2E1 inhibitor CMZ (Hu et al, 1994) or YH439 ( Jeong et al, 1996). In addition, general antioxidants such as SAMe and betaine were shown to preserve mitochondrial function and proteome in the animal models of AFLD Purohit et al, 2007) and NAFLD (Santamaria et al, 2003), partly through blocking the ROS/RNS production and restoring the physiological levels of GSH, SAMe, and S-adenosyl-homocysteine.…”

Protective effect of wild Corni fructus methanolic extract against acute alcoholic liver injury in mice

“…Excessive ROS production caused by alcohol consumption can adversely affect proteins, lipids, and DNA [8], leading to hepatocyte damage. Previous studies showed that ALI was associated with an increase in alcohol-induced CYP2E1 activity, which caused oxidative stress and lipid peroxidation in ALI models [9,10].…”