ABSTRACT
Classical xenoestrogenic in vivo effects of bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) are well-described in the literature, however the molecular mechanisms of BPA-induced hepatotoxicity are not fully characterized. The work is aimed to assess biochemical markers of BPA induced hepatotoxicity under conditions of differential supplementation with retinoids. We demonstrate that the absence of hepatic retinyl esters as the main form of vitamin A storage provides for a resistance to BPA induced liver damage. Retinoid supplementation increases the hepatotoxic effects of bisphenol A, evidenced in higher indexes of oxidative damage of lipids, proteins and non-protein thiol groups as well as increase of serum alanine aminotransferase activity and myeloperoxidase activity in liver parenchyma. The absence of hepatotoxicity signs when hepatic retinoid stores are depleted and their presence during normal or excessive retinoid supplementation suggest that hepatic retinoid availability is one of the factors determining the hepatotoxicity of bisphenol A.
Subject(s)
Benzhydryl Compounds/toxicity , Chemical and Drug Induced Liver Injury/metabolism , Endocrine Disruptors/toxicity , Phenols/toxicity , Vitamin A/analogs & derivatives , Vitamin A/adverse effects , Acyltransferases/deficiency , Acyltransferases/genetics , Alanine Transaminase/blood , Alanine Transaminase/genetics , Animals , Chemical and Drug Induced Liver Injury/pathology , Diterpenes , Gene Expression , Liver/drug effects , Liver/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidative Stress , Peroxidase/genetics , Peroxidase/metabolism , Protein Carbonylation/drug effects , Retinyl Esters , Thiobarbituric Acid Reactive Substances/metabolism , Vitamin A/metabolismABSTRACT
Hepatoprotective activity of Nuclex, a pharmaceutical composed of low-molecular yeast RNA, was investigated during acute and chronic thioacetamide-induced hepatotoxicity. It is demonstrated, that Nuclex administration at a dose of 200 mg/kg during acute and chronic liver injury produces hepatoprotective effect, which is associated with decrease in liver parenchyma lesions and in its inflammatory infiltration. Nuclex application attenuates thioacetamide-induced free radical damage of hepatic biopolymers, expressed in the reduction of TBA-reactive products, carbonyl derivatives, and recovery of protein thiol groups and reduced glutathione levels.
