Hepatoprotective effects of glycyrrhizin and omega-3 fatty acids on Nuclear Factor-kappa B pathway in thioacetamide-induced fibrosis in rats

Abstract

Available online xxx Keywords:Liver fibrosis Glycyrrhizin Omega-3 fatty acids NF-kB MDA a b s t r a c t Nuclear Factor kappa B (NF-kB) is a key transcriptional regulator that plays important roles in the pathogenesis of hepatic inflammation and fibrosis in chronic liver diseases.NF-kB activation leads to production of pro-inflammatory and fibrogenic cytokines.Glycyrrhizin (GL) is reported to suppress liver fibrosis and cirrhosis. Omega-3 fatty acids (u-3) play an anti-inflammatory role and they are reported to decrease hepatic injury in Thioacetamide (TAA) fibrotic model. We investigated the effects of GL and u-3 on liver inflammation and fibrosis in rats and clarified the effects of these natural compounds on NF-kB level. 50 male Wistar rats randomized to 5 groups: Control group and 4 groups received TAA 200 mg/kg i.p. twice weekly for 8 weeks: TAA group, GL group (received GL 25 mg/kg daily by oral tube), u-3 group (received u-3150 mg/kg daily by oral tube), (GL þ u-3) group (received similar combined doses of both natural compounds). GL and u-3 alone or in combination protected the liver from TAA hepatotoxic effects as they significantly decreased serum AST activity and serum total bilirubin level, they also significantly increased serum albumin and total protein levels. The hepatoprotective effects of GL and u-3 were confirmed by the histopathological analysis as they significantly reduced the necroinflammatory scores and the extent of fibrosis. GL and u-3 significantly decreased liver malondialdehyde level (P < 0.005), liver NF-ƙB level (P < 0.005) and its tissue expression as detected by immunohistochemistry. In conclusion, glycyrrhizin and omega-3 fatty acids alone or in combination have potent antiinflammatory, anti-oxidant and anti-fibrotic effects.Please cite this article in press as: Abo El-Magd NF, et al., Hepatoprotective effects of glycyrrhizin and omega-3 fatty acids on Nuclear Factor-kappa B pathway in thioacetamide-induced fibrosis in rats, Egyptian Journal of Basic and Applied Sciences (2015), http://dx.

Potential Ameliorative Effects of Alpha Lipoic Acid and Silymarin on Thioacetamide-Induced Hepatic Damage in Rats

“…The histopathological alterations were confined to both hepatic cells and portal areas that showed moderate to great thickening by mononuclear cells infiltration and biliary epithelial hyperplasia and then progressed by the time giving more severe lesions at ten weeks post to involve bridging necrosis as well as markedly thickened and extended portal area giving the nodular appearance. Similar results were documented by Abo El-Magd et al (2015) and Osman (2016). Moreover, TAA intoxication disturbs lipid metabolism as our data revealed a significant elevation in serum TG and TC with a significant reduction in HDL in TAA-treated rats in addition to hepatocytic vacuolation of fatty type that were found at the ten weeks of the treatment (Mustafa et al, 2013).…”

Glycyrrhizin and Omega-3 fatty acids have hepatoprotective roles through toll-like receptor-4

“…In this study, TAA intoxication caused intense oxidative stress as evidenced by the dramatic increase in the hepatic MDA concentration. This was in consistence with a previous study [16,21]. Oxidative stress is believed to be a major participating factor in TAA-induced liver fibrosis.…”

Influence of Omega-3 and Green Tea Extract on Alcohol-Induced Liver Injury in Rats

“…In most cases, the improvement in bilirubin concentration was rapid and reached a normal level, whereas ALP concentration was not significantly decreased during the first 4 weeks after initiating therapy with omegaven [19], regarding STB and ALP, this agrees with the results of our study. Analysis of our data showed that administration of OMG-3 fish oil to alcohol-fed rats resulted in a significant increase in serum TP and ALB levels, these findings were in agreement with [41] who studied hepatoprotective activity of omega-3 fish oil against thioacetamide-induced fibrosis in rats. In addition [42], demonstrated that the increase in concentration of serum TP and ALB within the normal range in rabbits fed on economic control diet supplemented with 0.5 and 1.0 mL fish oil per day/kg live bodyweight may reflect an increase in the hepatic function when animals were fed on fish oil.…”