ascorbic-acid and Chemical-and-Drug-Induced-Liver-Injury--Chronic

We evaluated the long-term effects of green tea extract (GTE) supplementation on oxidative stress, biliary acute phase protein expression, and liver function in CCl(4)-induced chronic liver injury.. We evaluated the antioxidant activity of GTE in comparison with those of vitamin C, vitamin E, and β-carotene in vitro by using an ultrasensitive chemiluminescence analyzer. Chronic liver injury was induced by intraperitoneally administering carbon tetrachloride (CCl(4)) (1 mL/kg body weight, twice weekly) to female Wistar rats for 8 weeks. The effects of low (4 mg/kg body weight per day) and high (20 mg/kg body weight per day) doses of intragastric GTE on CCl(4)-induced liver dysfunction and fibrosis were examined by measuring the bile and blood reactive oxygen species levels and biochemical parameters by using Western blot and two-dimensional polyacrylamide gel electrophoresis techniques.. GTE has greater scavenging activity against O(2)(-), H(2)O(2), and Hypochlorous acid (HOCl) in vitro than vitamin C, vitamin E, and β-carotene do. In vivo, CCl(4) markedly increased bile and blood reactive oxygen species production, lipid accumulation, number of infiltrated leukocytes, fibrosis, hepatic hydroxyproline content, and plasma alanine aminotransferase and aspartate aminotransferase activities, and reduced plasma albumin levels. Two-dimensional polyacrylamide gel electrophoresis revealed that CCl(4) increased the acute-phase expression of six biliary proteins and decreased hepatic B-cell lymphoma 2 (Bcl-2), catalase, and CuZn superoxide dismutase protein expression. GTE supplementation attenuated CCl(4)-enhanced oxidative stress, levels of biochemical parameters, pathology, and acute-phase protein secretion, and preserved antioxidant/antiapoptotic protein expression.. GTE supplementation attenuates CCl(4)-induced hepatic oxidative stress, fibrosis, acute phase protein excretion, and hepatic dysfunction via the antioxidant and antiapoptotic defense mechanisms.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; beta Carotene; Bile; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury, Chronic; Female; Hydroxyproline; Lipid Metabolism; Liver Cirrhosis; Oxidative Stress; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Reactive Oxygen Species; Tea; Vitamin E

The aim of the present investigation was to study the effects of olive oil (OO), corn oil (CO), and flaxseed oil (FO), with or without supplementation of vitamins E and C, on food intake, body weight gain %, liver weight to body weight %, total lipids, liver functions, and liver histology in male rats intoxicated with carbon tetrachloride (CCl(4)). Forty-two rats were divided into two main groups. The first main group was fed on basal diet (BD) as a negative control group (NC). The second main group received subcutaneous injections of CCl(4) in paraffin oil (50% v/v 2 ml/kg) twice a week to induce chronic damage in the liver. The group was then divided into six subgroups, three of which were fed on 4% unsupplemented oils (CO, FO, and OO) as positive control for the three oils used. The rest of the groups were fed on 4% of the same oils supplemented with vitamins E and C. The results of the flaxseed oil rat group indicate that supplementing vitamin E and C led to a significant reduction in the mean values of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and liver alanine amino transferase enzyme (ALT). Moreover, it caused an increase of the mean value of high-density lipoprotein cholesterol (HDL-C) as compared to the negative control group (NC). The olive oil group supplemented with the same vitamins showed a significant decrease in the mean value of serum TC and significant (P<0.05) increase in the mean value of serum HDL-C as compared to NC. The results of the corn oil group supplemented with vitamins showed a significant increase in the mean value of serum HDL-C as compared to the negative control group. The histology results confirmed that the group hepatically injured with CCl(4) treatment and fed on supplemented FO or OO showed apparently normal hepatocytes.. The most effective treatment was observed with oils supplemented with vitamins E and C. Hierarchically FO achieved the best results compared to other additives, followed by OO and finally CO showing the least effective treatment among the observed groups.

Topics: Animals; Ascorbic Acid; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury, Chronic; Dietary Supplements; Disease Models, Animal; Drug Combinations; Lipids; Liver Function Tests; Male; Nutritional Status; Oils; Rats; Rats, Sprague-Dawley; Treatment Outcome; Vitamin E

After 12, 18, and 24 h of oral administration of carbon tetrachloride (as a 1:1 mixture with mineral oil: 4 ml/kg body weight) to rats, the activity of caspase-3-like protease in the liver increased significantly compared to that in the control group that was given mineral oil (4 ml/kg). In plasma, the activity of caspase-3 was barely detectable in the control rat, but increased significantly 24 h after drug administration along with a dramatic increase in glutamate oxaloacetate transaminase. These results indicate that carbon tetrachloride causes apoptosis in the liver by activating caspase-3, which is released to plasma by secondary necrosis. After 18 and 24 h of carbon tetrachloride administration, the liver concentration of hydrophilic vitamin C was decreased significantly, while that of hydrophobic vitamin E was not affected. The plasma concentration of vitamins C and E was not influenced significantly. These results suggest that carbon tetrachloride induces oxidative stress mainly in the aqueous phase of the liver cell.

Topics: Animals; Apoptosis; Ascorbic Acid; Carbon Tetrachloride; Caspase 3; Caspases; Chemical and Drug Induced Liver Injury, Chronic; Enzyme Activation; Liver; Male; Necrosis; Oxidative Stress; Rats; Rats, Sprague-Dawley; Time Factors; Vitamin E