The Protective Role of Tomato Powder in the Toxicity, Fatty Infiltration and Necrosis Induced by Oxidized Tallow in Rabbits : PROTECTIVE ROLE OF TOMATO POWDER

Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species (ROS) and liver damage, whereas JNK1 activation promotes ROS accumulation, liver damage, and carcinogenesis. We examined whether hepatocyte p38 alpha, found to inhibit liver carcinogenesis, acts similarly to IKK beta in control of ROS metabolism and cell death. Hepatocyte-specific p38 alpha ablation enhanced ROS accumulation and liver damage, which were prevented upon administration of an antioxidant. In addition to elevated ROS accumulation, hepatocyte death, augmented by loss of either IKK beta or p38 alpha, was associated with release of IL-1 alpha. Inhibition of IL-1 alpha action or ablation of its receptor inhibited carcinogen-induced compensatory proliferation and liver tumorigenesis. IL-1 alpha release by necrotic hepatocytes is therefore an important mediator of liver tumorigenesis.

Tumor necrosis factor (TNF)alpha, a pivotal cytokine involved in inflammation, is produced primarily by Kupffer cells in the liver. It has been shown that inactivation of Kupffer cells prevents alcohol-induced liver injury; therefore, the purpose of this study was to determine if neutralizing anti-TNF-alpha antibody is also effective. Male Wistar rats were exposed to ethanol (11 to 12 g x kg(-1) x d[-1]) continuously for up to 4 weeks via intragastric feeding using an enteral feeding model. Before ethanol exposure, polyclonal anti-mouse TNF-alpha rabbit serum was injected (2.0 mg/kg intravenously). There were no significant differences in body weight, mean ethanol concentration, or cyclic patterns of ethanol in urine when ethanol- and ethanol plus antibody-treated groups were compared. Expression of TNF-alpha and macrophage inflammatory protein 2 (MIP-2) messenger RNA (mRNA), determined using reverse transcription-polymerase chain reaction, was three- to four-fold higher in livers of ethanol-treated rats than in those of rats fed an ethanol-free, high-fat control diet. In addition, MIP-2 levels were also elevated when detected by Northern blot analysis. Anti-TNF-alpha antibody did not affect expression of mRNA for interleukin (IL) 1alpha, IL-6, transforming growth factor beta1, or TNF-alpha. However, MIP-2 mRNA expression, which is regulated by TNF-alpha, was decreased significantly by anti-TNF-alpha antibody treatment. Serum aspartate transaminase levels were elevated in ethanol-treated rats to 136 +/- 12 IU/L after 4 weeks but only reached 90 +/- 5 IU/L (P < .05) in rats treated with anti-TNF-alpha antibody. The hepatic inflammation and necrosis observed in ethanol-fed rats were attenuated significantly by antibody treatment, and steatosis was not. These results support the hypothesis that TNF-alpha plays an important role in inflammation and necrosis in alcohol-induced liver injury and that treatment with anti-TNF-alpha antibody may be therapeutically useful in this disease.

During the last half-century, the fruit of the cultivated tomato (Lycopersicon esculentum), commonly considered a vegetable, has become a popular and highly consumed food in the United States. Production of tomatoes in the United States ranks second only to potatoes. As a consequence, tomatoes and tomato-based foods provide a convenient matrix by which nutrients and other health-related food components can be supplied to human beings. Tomatoes and tomato products are rich sources of folate, vitamin C, and potassium. Relative to phytonutrients, the most abundant in tomatoes are the carotenoids. Lycopene is the most prominent carotenoid followed by beta-carotene, gamma-carotene and phytoene as well as several minor carotenoids. The antioxidant activity of lycopene as well as several other carotenoids and their abundance in tomatoes makes these foods rich sources of antioxidant activity. The provitamin A activity of beta- and gamma-carotene, their modest levels in tomato products, and the high consumption of these foods results in a rich supply of vitamin A activity from tomato-based foods. Tomatoes also contain several other components that are beneficial to health, including vitamin E, trace elements, flavonoids, phytosterols, and several water-soluble vitamins.