Revista de Toxicología Clínica
Acceso abierto

abstracto

Las toxinas THS inducen esteatosis hepática al alterar el estrés oxidativo y SIRT1 Niveles

Cristina Flores, Neema Adhami y Manuela Martins-Green

Background: Third hand smoke (THS) forms when second hand smoke (SHS) tobacco toxins accumulate on surfaces such as walls, carpets and clothing and can result in adverse health effects. Objective: This study was designed to investigate the mechanism of THS-induced hepatic steatosis. Methodology: We used an in vivo exposure system that mimics exposure of humans to THS to investigate the effects of THS on hepatic lipid metabolism. THS-exposed mice were treated either with the liver-damaging drug, Nacetyl- p-aminophenol (APAP/Tylenol) to increase oxidative stress or with the antioxidants N-acetyl-cysteine and α- Tocopherol which decrease oxidative stress. Results: THS-exposed mice have higher levels of superoxide dismutase activity and H2O2 levels. However, no significant changes in activity of the antioxidant enzymes catalase and glutathione peroxidase were found, implying the presence of high levels of hydrogen peroxide in the liver. Furthermore, THS-exposed mice also have a lower NADP+/NADPH ratio, indicating decreased ability of these mice to combat oxidative stress. THS-exposed mice show a decrease in ATP production, increase in aspartate aminotransferase (AST) activity, as well as increased molecular damage (lipid peroxidation, protein nitrosylation and DNA damage). Treating THS-exposed mice with APAP/Tylenol enhances the THS-induced damage whereas treating with antioxidants reduces the damage. THSexposed mice also have lower sirtuin 1 (SIRT1) levels compared to controls which decreased activation of 5' AMPactivated protein kinase (AMPK) and increased sterol regulatory element binding protein 1c (SREBP1c). Conclusion: THS-exposed mice on a normal diet have increased oxidative stress and damage mediated by oxidative stress, which results in alterations to the SIRT1/AMPK/SREPB1c signaling pathway. Increasing oxidative stress results in enhanced THS-induced damage whereas decreasing oxidative stress causes improvement in the THS-induced liver damage. Our results show that THS is a new risk factor contributing to the development of liver steatosis and highlight the danger of THS in general.