Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.

Cultured rat hepatocytes and human hepatoma HepG2 cells were used to evaluate the hepatoprotective properties of polyphenolic extracts from the edible part of artichoke (AE). The hepatocytes were exposed to H2O2generated in situ by glucose oxidase and were treated with either AE, or pure chlorogenic acid (ChA) or with the well known antioxidant, N, N'-diphenyl-p-phenilenediamine (DPPD). Addition of glucose oxidase to the culture medium caused depletion of intracellular glutathione (GSH) content, accumulation of malondialdehyde (MDA) in the cultures, as a lipid peroxidation indicator, and cell death. These results demonstrated that AE protected cells from the oxidative stress caused by glucose oxidase, comparable to DPPD. Furthermore, AE, as well as ChA, prevented the loss of total GSH and the accumulation of MDA. Treatment of HepG2 cells for 24 h with AE reduced cell viability in a dose-dependent manner, however, ChA had no prominent effects on the cell death rate. Similarly, AE rather than ChA induced apoptosis, measured by flow cytometric analysis of annexin and by activation of caspase-3, in HepG2 cells. Our findings indicate that AE had a marked antioxidative potential that protects hepatocytes from an oxidative stress. Furthermore, AE reduced cell viability and had an apoptotic activity on a human liver cancer cell line.

Reactive oxygen species (ROS) produced by inflammatory cells can contribute to tissue destruction. ROS

This study examines nutritional status and clinical outcomes, including pressure ulcers and death in 40 chronically tube-fed long-term care patients. Anthropometric, biochemical, clinical and dietary data were collected over a 3-month period, with follow-up of mortality at 1 year. Subjects' functional and cognitive status was generally poor. Adequate calories and protein were provided, with sample means exceeding standard means for energy, protein and micronutrients. Still, subjects showed weight loss and severe depletion of lean and fat body mass. Mean serum protein and micronutrient status measures were in the low normal range. Hemoglobin, hematocrit, and serum zinc and carotenoid levels were below normal in a sizable proportion of patients. Pressure ulcers were present in 65% of patients. Weight loss was associated with longer time on tube feeding and more pressure ulcers. Negative correlations with ulcer number were observed for cholesterol, albumin, zinc, retinol, alpha-tocopherol and iron. This study shows that despite administration of apparently adequate formula, micronutrient deficiencies and marasmic malnutrition exist in chronically ill patients. Causes may include the combined effects of chronic disease, sepsis, immobility, and severe neurologic deficits. Clinical outcomes may be expressions of an organism-wide diminution of protein synthesis, the cause of which is unknown. For clinical management, serial measures of weight, albumin, cholesterol, hemoglobin and hematocrit are recommended. Future research must address the many subsets of the population of chronically tube-fed patients.

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