Pyridoxamine improves metabolic and microcirculatory complications associated with nonalcoholic fatty liver disease

• Published in: Microcirculation (New York, N.Y. 1994) Vol. 27; no. 3; pp. e12603 - n/a
• Main Authors: Pereira, Evelyn Nunes Goulart da Silva, Silvares, Raquel Rangel, Flores, Edgar Eduardo Ilaquita, Rodrigues, Karine Lino, Daliry, Anissa
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2020
• Subjects: advanced glycation end products; Animals; Diet, High-Fat - adverse effects; Lipid Peroxidation - drug effects; Liver - blood supply; Liver - metabolism; Liver - physiopathology; Liver diseases; Male; Metabolism; microcirculation; Microcirculation - drug effects; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - physiopathology; nonalcoholic fatty liver disease; Oxidative stress; Oxidative Stress - drug effects; pyridoxamine; Pyridoxamine - pharmacology; Rats; Rats, Wistar; Tumor necrosis factor-TNF; pyridoxamine; nonalcoholic fatty liver disease; advanced glycation end products; microcirculation
• ISSN: 1073-9688; 1549-8719
• DOI: 10.1111/micc.12603

Objective We investigated the protective effects of pyridoxamine against metabolic and microcirculatory complications in nonalcoholic fatty liver disease. Methods Nonalcoholic fatty liver disease was established by a high‐fat diet administration over 28 weeks. Pyridoxamine was administered between weeks 20 and 28. The recruitment of leukocytes and the number of vitamin A‐positive hepatic stellate cells were examined by in vivo microscopy. Laser speckle contrast imaging was used to evaluate microcirculatory hepatic perfusion. Thiobarbituric acid reactive substances measurement and RT‐PCR were used for oxidative stress and inflammatory parameters. advanced glycation end products were evaluated by fluorescence spectroscopy. Results The increase in body, liver, and fat weights, together with steatosis and impairment in glucose metabolism observed in the nonalcoholic fatty liver disease group were attenuated by pyridoxamine treatment. Regarding the hepatic microcirculatory parameters, rats with high‐fat diet‐induced nonalcoholic fatty liver disease showed increased rolling and adhesion of leukocytes, increased hepatic stellate cells activation, and decreased tissue perfusion, which were reverted by pyridoxamine. Pyridoxamine protected against the increased hepatic lipid peroxidation observed in the nonalcoholic fatty liver disease group. Pyridoxamine treatment was associated with increased levels of tumor necrosis factor alpha (TNF‐α) mRNA transcripts in the liver. Conclusion Pyridoxamine modulates oxidative stress, advanced glycation end products, TNF‐α transcripts levels, and metabolic disturbances, being a potential treatment for nonalcoholic fatty liver disease‐associated microcirculatory and metabolic complications.