Papel de produtos finais de glicação avançada nas alterações hepáticas e metabólicas em modelo experimental de síndrome metabólica

Non-alcoholic fatty liver disease (NAFLD) affect one-third of the adult population, and is defined as the accumulation of fat in the liver of patients who do not consume excessive alcohol. However, the molecular mechanisms that account for disease progression remains unclear. Previous studies have demonstrated that the increase in liver advanced glycation end-products (AGEs) levels and microcirculatory disturbances are present in NAFLD however no direct evidence of the link between AGE levels, oxidative stress, inflammatory pathways and hepatic microcirculatory alterations have been demonstrated. We investigated the protective effects of pyridoxamine (1) against metabolic and microcirculatory complications in NAFLD. NAFLD was induced by a high-fat diet (HFD) administration over 28 weeks. Pir treatment was administered between weeks 20 and 28. In the liver microcirculation, the recruitment of leukocytes and the number of vitamin A positive hepatic stellate cells (HSCs) were examined by in vivo microscopic observations. Tissue perfusion was accessed by laser speckle contrast imaging (LSCI) Oxidative stress and inflammatory parameters were assessed by thiobarbituric acid reactive substances measurement (TBARs) and RT-PCR. AGEs in the liver were evaluated by fluorescence spectroscopy. The increase in body, liver, and fat weight observed in the NAFLD group was reverted by Pir treatment. High-fat diet administration induced steatosis and impairment in glucose metabolism, which were attenuated by Pir treatment. Regarding the hepatic microcirculatory parameters, rats with HFD-induced NAFLD showed increased rolling and adhesion of leukocytes, increased HSC activation and decreased tissue perfusion. Pir showed a vasoprotective effect in the hepatic microcirculation of HFD-induced NAFLD. Livers of NAFLD group of rats had elevated levels of lipid peroxidation, which were partially reverted by the Pir treatment. Pir modulates oxidative stress, AGEs, and/or other metabolic disturbances, thus providing important vasoprotective effects. Therefore, Pir may be a potential treatment for microcirculatory and metabolic complications associated with NAFLD