N-acetyl cysteine prevents alterations generated during experimental liver steatosis induced by a chronic consumption of alcohol plus a hypercaloric diet.

Abstract

Introduction and Objectives: : Metabolic alterations and alcohol consumption are the most common etiological agents related to hepatic steatosis (HS) development. There is little evidence that shows the effects generated by synergy of both etiologic agents. N-acetyl cysteine (NAC) is a drug whose efficacy in the early stages of SH, generated by a hypercaloric diet plus alcohol consumption, is unknown.The aim of this work was to evaluate NAC effects on oxidative stress, and metabolic alterations induced in HS experimentally induced by chronic ethanol consumption plus a hypercaloric diet. Materials and Patients: C57BL/6J mice (n=4) grouped into 1) Control; 2) HF/OH, administrated with hypercaloric diet and ethanol; 3) HF/OH+NAC, same treatments of group 2 plus NAC. Serum markers of liver damage and anorexigenic and orexigenic adipokines were evaluated; oxidative stress markers in liver samples were analyzed; finally, a H&E stain was performed. This project was conducted in accordance with the guidelines of the University of Guadalajara under the approval number of the bioethics, research, and ethics research committees CI-02920. Results: NAC prevents weight gain and metabolic alterations generated by concomitant consumption of a hypercaloric diet and alcohol; this drug improves changes in anorexigenic and orexigenic adipokines such as leptin, ghrelin, resistin, GLP-1, and modulates total, HDL, and LDL cholesterol levels. On the other hand, NAC reduces CYP2E1 and alcohol dehydrogenase expression, as well as the oxidative environment induced by both etiological agents, by avoiding an increase in malondialdehyde levels, promoting Nrf2 transcription factor expression and superoxide dismutase; also preventing an increase in the expression of Catalase. Finally, H&E staining showed that NAC prevents the development of tissue alterations in the liver parenchyma generated by the consumption of a hypocaloric diet plus alcohol. Conclusions: In this work, we demonstrate that NAC prevents metabolic alterations and oxidative damage related to early phases of HS induced by concomitant consumption of alcohol plus a hypercaloric diet. These effects would slow down the development of more severe stages of this disease.