Antioxidant effects of aqueous extract of Salep on Paraquat-induced rat liver injury

AIM To evaluate the effects of aqueous extract of Salep on Paraquat-mediated liver injury.METHODS In this experimental study, 56 adult male Wistar rats were divided randomly to 7 groups as control, sham, and 5 experimental groups. In control group, rats did not receive any substance during experiment. In Sham group, rats were given distilled water according to their body weight and in experimental groups, Paraquat alone and with different doses of Salep aqueous extract(40, 80, 160 and 320 mg/kg) was given intraperitoneal daily for 14 d. After that, liver biochemical parameter and histologic changes were analyzed and compared in different groups. RESULTS Paraquat compared to control and sham groups, significantly(P < 0.05) increased serum level of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), bilirubin, malondialdehyde(MDA) and total oxidant capacity(TOC); while level of total protein, albumin and total antioxidant capacity(TAC) were remarkably decreased by Paraquat. Salep at doses of 80, 160 and 320 mg/kg significantly decreased serum level of ALT, AST, ALP, bilirubin, MDA and TOC and significantly increased total protein, albumin and TAC level as compared to Paraquat exposed group in dose dependent manner. Aqueous extract of Salep at doses of 40 mg/kg made no significant changes in serum level of mentioned biochemical parameters. Liver microscopic observation revealed that Paraquat could cause hepatocyte necrosis, degenerative changes, proliferation and activation of Kupffer cells(sporadically) which were reduced by Salep treatment. CONCLUSION Salep possesses remarkable hepatoprotection activity against Paraquat-induced hepatic injury by having antioxidant activity and reducing lipid peroxidation and oxidative stress.

Effect of Genistein in Comparison with Trichostatin A on Reactivation of DNMTs Genes in Hepatocellular Carcinoma

Background and Aims:DNA methylation and histone mod-ification are epigenetic modifications essential for normal function of mammalian cells.The processes are mediated by biochemical interactions between DNA methyltransferases(DNMTs)and histone deacetylases.Promoter hypermethyla-tion and deacetylation of tumor suppressor genes play major roles in cancer induction,through transcriptional silencing of these genes.DNA hypermethylation is carried out by a family of DNMTs including DNMT1,DNMT3a and DNMT3b.In hepatocellular carcinoma,a significant positive correlation bet-ween over-expression of these genes and cancer induction has been reported.The DNA demethylating agent genistein(GE)has been demonstrated to reduce different cancers.Pre-viously,we reported that GE can induce apoptosis and inhibit proliferation in hepatocellular carcinoma PLC/PRF5 and HepG2 cell lines.Besides,histone deacetylase inhibitors,such as trichostatin A(TSA),were successfully used to inhibit cancer cell growth.The present study was designed to assess the effect of GE in comparison with TSA on DNMT1,DNMT3a and DNMT3b gene expression,cell growth inhibition and apoptosis induction in the HepG2 cell line.Methods:Cells were seeded and treated with various doses of GE and TSA.The MTT assay,flow cytometry assay,and real-time RT-PCR were used to determine viability,apoptosis,and DNMT1,DNMT3a and DNMT3b gene expression respectively.Results:Both agents inhibited cell growth,induced apoptosis and re-activated DNMT1,DNMT3a and DNMT3b gene expression.Furthermore,TSA demonstrated a significantly greater apop-totic effect than the other agent,whereas GE improved gene expression more significantly than TSA.Conclusions:Our findings suggest that GE and TSA can significantly inhibit cell growth,induce apoptosis and restore DNMT1,DNMT3a and DNMT3b gene reactivation.