Stimulatory effect of Silibinin on the DNA synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malign cell lines

Acrylamide is a carcinogenic, mutagenic and reprotoxic substance to humans through the intense oxidative stress it induces. As the liver is the most important organ in detoxifying toxic agents, we investigated here the hepatoprotective potential of Thymus satureioides aerial parts extract and their essential oil, profiled by LC–MS/MS and GC–MS, respectively, on acrylamide-induced liver toxicity in vivo. Adult male Wistar albino rats were randomly assigned into six equal groups, namely the negative control group (10% w/v gum acacia and corn oil), the acrylamide group (10% gum acacia and corn oil + acrylamide (25 mg/kg/day)), T. satureioides polyphenols-treated group (100 and 200 mg/kg/day + acrylamide (25 mg/kg/day)), T. satureioides essential oil-treated group (EO, 0.25 ml/kg/day + acrylamide (25 mg/kg/day)), and silymarin group (Positive control) (100 mg/kg/day + acrylamide (25 mg/kg/day)). Liver toxicity was monitored by measuring liver enzyme activities, oxidative stress markers, NLRP3 inflammasome and inflammatory markers, apoptosis signaling, immunohistochemical study and morphometric analysis. Acrylamide administration substantially elevated serum liver enzymes AST, ALT, and serum total bilirubin, altered liver architecture, decreased hepatic GSH, increased hydropic cells scoring, collagen fibre deposition, immunoexpression of liver fibrotic markers (MMP9 and TGF-1β), lipid peroxidation (MDA), inflammatory responses (IL-1β and p38 MAPK) in hepatic tissues, upregulated liver NLRP3 inflammasome activation, and augmented NF-κB and caspase 3 signaling pathways. These toxicity manifestations were significantly counteracted when rats were pretreated with either T. satureioides polyphenolics or EO as well as silymarin, the reference hepatoprotective compound. Both the polyphenolics and EO furnished comparable mitigation effects to those obtained using silymarin. The observed hepatoprotective activities could be attributed to presence of diverse metabolites (EO (39 compounds) and the extract (45 compounds)) with pronounced antioxidant and anti-inflammatory activities. This study strongly shows the effectiveness of T. satureioides polyphenolics and essential oil in mitigating acrylamide-induced liver toxicity.