stilbenes and Carbon-Tetrachloride-Poisoning

Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection. Unfortunately, RES is restricted in clinical application due to poor dissolution property and adsorption. In addition, red wine as a supplement for preventing disease is not recommended for patients with alcohol-related disorders. To address these limitations, we successfully developed a novel RES nanoparticle system (RESN) and demonstrated that RESN could circumvent the physicochemical drawbacks of raw RES with respect to dissolution, such as the reduction of particle size, amorphous transformation, and hydrogen-bond formation. In addition, we employed an animal model of CCl₄-induced hepatotoxicity to estimate the potential of the nanoparticle formulation to improve the hepatoprotective effect of orally administered RES. Our results demonstrated that RESN can diminish liver function markers (aspartate aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due to CCl₄-induced hepatotoxicity in rats, when compared with RES administration. The effect was achieved by reducing oxidative stress (decreased reactive oxygen species and lipid peroxidation) and lowering inflammatory cytokines (decreased tumor necrosis factor-α and interleukin 1β) and protein expression (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2, and caspase-3). In conclusion, enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carbon Tetrachloride Poisoning; Drug Delivery Systems; Liver; Male; Nanoparticles; Rats; Rats, Wistar; Resveratrol; Solubility; Stilbenes

The importance of hydroxyl groups in the antioxidant and hepatoprotective properties of resveratrol was investigated. To achieve this, resveratrol or its trimethylated analog were administered (10 mg kg(-1), p.o.) to male Wistar rats and liver damage was induced by acute administration of CCl4 (4 g kg(-1), p.o.); appropriate controls were performed. The animals were killed 24 h after CCl4 intoxication. The amount of reduced glutathione (GSH) in the liver was not modified by any treatment; interestingly, the GSH/GSSG (oxidized glutathione) ratio decreased in the groups receiving CCl4 and resveratrol associated with an increase in GSSG. In blood GSH and the GSH/GSSG ratio were decreased by CCl4; both effects were completely prevented by any of the compounds tested. Lipid peroxidation and the activity of gamma-glutamyl transpeptidase were increased significantly after CCl4. Resveratrol partially prevented these increases and surprisingly, trimethylated resveratrol completely prevented the increase of these markers. Both compounds partially but significantly prevented the increase in the activity of alanine aminotransferase; this result agrees with observations in the histological analysis. Both tested compounds administered alone produced no effect. The results of the present study suggest that OH groups are important for the antioxidant and hepatoprotective properties of the molecule of resveratrol; nevertheless, these effects can be improved by replacing hydrogen by a methyl in these groups. The differences in the antioxidant and hepatoprotective effects of these compounds could be due to the possibility that the trimethylated resveratrol acts like a prodrug, prolonging, probably, the half-life of the original compound.

Topics: Acute Disease; Alanine Transaminase; Animals; Antioxidants; Carbon Tetrachloride Poisoning; Disease Models, Animal; gamma-Glutamyltransferase; Glutathione; Glutathione Disulfide; Lipid Peroxidation; Liver; Liver Diseases; Male; Methylation; Molecular Structure; Rats; Rats, Wistar; Resveratrol; Stilbenes; Structure-Activity Relationship

To study the protective effect of Gn-3 (a stilbene polymer isolated from Gnetum parvifolium) against liver injury induced by CCl4, N-acetyl-p-aminophenol (APAP) and Bacillus Calmette-Guerin (BCG) plus bacterial lipopolysaccharide (LPS) in mice.. The experimental model of liver injury were induced by 0.1% CCl4 i.p. (10 mL.kg-1.d-1 for 3d), APAP i.p. (150 mg.kg-1) or BCG (5 mg) plus LPS (7.5 micrograms) in mice. The levels of ALT in serum, MDA and GSH in liver tissues were detected. The histopathologic changes were observed by light microscope.. Gn-3 was shown to markedly reduce the elevated serum ALT levels, liver tissue MDA and improve the histopathological changes in all the three experimental liver injury models. No effect of Gn-3 was observed on the liver GSH level in liver injury mice.. Gn-3 was found to inhibit the development of liver injury caused by CCl4, APAP, or BCG plus LPS. This means that Gn-3 has liver protective effects.

Topics: Acetaminophen; Alanine Transaminase; Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Gnetum; Lipopolysaccharides; Liver; Male; Malondialdehyde; Mice; Mycobacterium bovis; Plants, Medicinal; Protective Agents; Random Allocation; Stilbenes

The methanol extract of the Oriental medicinal plant Vitis coignetiae (Vitaceae) showed hepatoprotective activity in the in vitro assay method using primary cultured rat hepatocytes. Activity-guided fractionation of the extract afforded epsilon-viniferin as an active principle. The protective effect of epsilon-viniferin against mice carbon tetrachloride-induced hepatic injury in mice was shown by serum enzyme assay as well as by pathological examination. In addition to epsilon-viniferin, plant oligostilbenes, ampelopsins A, C, F and the mixture of vitisin A and cis-vitisin A were also present in the extract. Among them, ampelopsin C and the mixture of vitisin A and cis-vitisin A were found to be powerful hepatotoxins.

Topics: Animals; Benzofurans; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver Diseases; Male; Mice; Molecular Structure; Plants, Medicinal; Stilbenes

Topics: Alanine Transaminase; Animals; Carbon Tetrachloride Poisoning; Liver; Liver Glycogen; Male; Mice; Rats; Stilbenes