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The protective role of ellagitannins flavonoids pretreatment against N-nitrosodiethylamine induced-hepatocellular carcinoma

Hussein, Rasha H., Khalifa, Fares K.
Saudi Journal of Biological Sciences 2014 v.21 pp. 589-596
diethylnitrosamine, aspartate transaminase, bilirubin, hepatoma, chemoprevention, flavonoids, oral administration, oxidative stress, protective effect, glutathione, glucose, alanine transaminase, glutathione transferase, esters, alpha-L-fucosidase, arginase, NADP-glucose-6-phosphate dehydrogenase, blood proteins, models, ellagic acid, gamma-glutamyltransferase, rats, enzyme activity, antioxidant activity, antioxidants, liver, DNA fragmentation, carcinoma, glutathione peroxidase, alkaline phosphatase
Ellagitannins are esters of glucose with hexahydroxydiphenic acid; when hydrolyzed, they yield ellagic acid (EA), the dilactone of hexahydroxydiphenic acid. EA has been receiving the most attention, because it has potent antioxidant activity, radical scavenging capacity, chemopreventive and antiapoptotic properties. Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of liver, and accounts for as many as one million deaths worldwide in a year. The aim of the present study was to evaluate the antioxidant and chemopreventive efficiency of ellagic acid against N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in rats. Rats were classified into four groups as follows: normal control group, group injected i.p. with a single dose (200mg/kgb.wt.) of NDEA, third group daily administered orally EA with a dose of 50mg/kgb.wt. for 7days before and 14days after NDEA administration, and fourth group received a similar dose of EA for 21days after the dose of NDEA administration. The model of NDEA-injected hepatocellular carcinomic (HCC) rats elicited significant declines in liver antioxidant enzyme activities; glutathione peroxidase (GPX), gamma glutamyl transferase (γ-GT) and glutathione-S-transferase (GST), with a reduction in reduced glutathione (GSH) and serum total protein with concomitant significant elevations in tumor markers arginase and α-l-fucosidase, and liver enzymes; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PD), direct and total bilirubin. The oral administration of EA as a protective agent, produced significant increases in tested antioxidant enzyme activities and serum total protein concomitant with significant decreases in the levels of tumor markers arginase and α-l-fucosidase as well as liver enzymes, direct and total bilirubin. Similarly, the oral administration of EA, as a curative agent produced similar changes to those when EA was used as a protective agent, but to a lesser extent. In addition, it was noted that HCC rats exhibited a degree of DNA fragmentation; however, EA administration partially inhibited the DNA fragmentation. Therefore, EA has the ability to scavenge free radicals, prevent DNA fragmentation, reduce liver injury and protect against oxidative stress.