Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism

Background and the purpose of the study: Silymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated. Methods: We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-alpha and TGF-beta 1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month). Results: A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-beta 1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin. Conclusion: This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-alpha on the effectiveness of silymarin might be used for individualize therapy.