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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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Assessment of the cytotoxix effects of selected transdermal permeation enhancers in keratinocytes
Wojnarová, Lea ; Šimůnek, Tomáš (advisor) ; Vávrová, Anna (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciencis Candidate: Lea Wojnarová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Assessment of the cytotoxic effects of selected transdermal permeation enhancers in keratinocytes Only a few drugs are able to permeate through the skin and reach therapeutic concentration in the systemic circulation. One method to enable transdermal administration can be the use of accelerants transdermal penetration. These substances affect different mechanisms and reversibly reduce the barrier properties of the skin. Substances which are used in clinical practice must fulfill strict criteria which include: efficiency and compatibility of the drug and accelerants; it must be non-toxic; non- irritating and without own pharmacological effect. In our research we studied selected transdermal penetration enhancers, namely Azone, dodecanol, DDAIP, DDAK, Transkarbam 12 and new derivatives of amino acids proline - LP12/2 and DP12/2 enantiomers and sarcosine - 12Sar2. The aim of our study was to determine the cytotoxicity effect of accelerants and assess whether the apoptosis was activated. These effects were studied using the keratinocyte cell line HaCaT. To determine the cytotoxic properties of accelerants,...
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