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Pharmacological perspectives and clinical benefits of SIRT1 and AMPK activators and inhibitors in inflammatory and oxidative stress in the liver
Njeka Wojnarová, Lea ; Kutinová Canová, Nikolina (advisor) ; Hodek, Petr (referee) ; Votava, Martin (referee)
Introduction: Liver diseases represent a significant cause of morbidity and mortality worldwide. Previous experimental studies have shown that polyphenolic compound, resveratrol, as a less specific activator of sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) can effectively attenuate acute liver injury. Although SIRT1 and AMPK have been widely studied for many years, further evidence for a mutual SIRT1/AMPK signaling mechanism and how it is modulated by drugs of small molecules had not been fully clarified at start of our experimental work. Goal: The main objective of the presented research was to investigate the relationship of SIRT1 and AMPK in process of hepatotoxicity/hepatoprotection in in vivo and in vitro animal model of acute drug-induced liver injury. Methods: Male Wistar rats were used for both in vivo and in vitro studies. Hepatotoxicity was induced by a single dose of D-Galactosamine (GalN)/lipopolysaccharide (LPS) or acetaminophen (APAP). Some rats and cultured hepatocytes were treated by resveratrol, synthetic selective activator or inhibitor of SIRT1 and AMPK. Biochemical markers of liver injury (aminotransaminases, total bilirubin), oxidative stress (nitrites) and lipid peroxidation (conjugated dienes, TBARS) were measured in the plasma, medium or liver homogenate. Liver...
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