Ameliorative effect of Silybin on bisphenol A induced oxidative stress, cell proliferation and steroid hormones oxidation in HepG2 cell cultures

Abstract

Bisphenol A (BPA) and silybin are considered xenoestrogens and could interfere with the action of endogenous hormones. It was demonstrated a higher level of BPA in plasma of nonalcoholic steatohepatitis (NASH) patients, compared to those with steatosis (NAFL). We investigated the effect of BPA and silybin, alone or in combination, on proliferation, oxidative stress and steroid metabolism in HepG2 grown in high glucose concentration medium (H-HepG2). Cell viability was assessed by adding 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). TBARS were quantified by spectrophotometry. The effect of BPA, silybin and their combination on the expression of phosphorilized extracellular signal-regulated kinase (ERK), ERK and Caspase 3 was determined by Western blot analysis. The identifications of lipids and steroid hormones was performed by mass spectrometry. BPA elicited in H-HepG2 oxidative stress and steroid hormones oxidation leading to the formation of metabolite with estrogenic and genotoxic potentials. Silybin ameliorates the harmful BPA-induced effect decreasing glucose uptake and lipid peroxidation. Moreover silybin activates the synthesis of vitamin D3 metabolites and prevent the steroid hormones oxidation. BPA could be considered as an important risk factor in worsening and progression of NAFLD. At the same time silybin could be a valid support to counteract these effects in NASH patients.

Fundamental Concepts and Novel Aspects of Polycystic Ovarian Syndrome: Expert Consensus Resolutions

“…It may develop into cirrhosis and hepatic failure, and therefore, its identification and treatment are of importance in patients with PCOS. A large body of in vitro evidence supports the direct benefit of incubation with silybin on hepatocytes in NAFLD models, mainly due to its capacity to reverse lipid accumulation in the liver (166)(167)(168). A controlled study in 90 NAFLD patients and 30 healthy controls reported the effectiveness of 6-month administration of silybin, vitamin D, and vitamin E on NAFLD fibrosis score, metabolic markers, oxidative stress, and endothelial dysfunction (169).…”

Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma

“…A mixture of flavonolignans and minor polyphenolic compounds derived from the milk thistle plant (Silybum marianum) named silymarin has been shown to have antioxidant power [137]. The main component of silymarin, silybin, has been shown to restore nicotinamide adenine dinucleotide (NAD+) levels, decreasing the glucose uptake and lipid peroxidation and resulting in the improvement of NAFLD [138,139]. Silymarin was shown to be effective for improving NASH-related fibrosis in a randomized, double-blind, placebo-controlled study, although the number of patients was relatively small (49 for silymarin and 50 for placebo) [140].…”

Chemical Effect of Bisphenol A on Non-Alcoholic Fatty Liver Disease

“…The aforementioned considerations lead to underlining the existing link between EDCs, their widespread diffusion, and their potential human health harmful effects. Several epidemiological and experimental studies suggested a strong relationship between EDCs exposure and the pathogenesis of Insulin Resistance (IR) associated diseases (a part from T2DM), such as poly-cystic ovary syndrome (PCOs), non-alcoholic fatty liver disease (NAFLD), and obesity [10,11,12,13].…”

“…Over the years, the amount of scientific evidence proving a direct correlation between EDCs exposure and adverse health effects, including neurodegenerative, cardiovascular, bone and immune diseases, and disorders of the reproductive or metabolic system, has exponentially grown [11,12].…”