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Lipid emulsions in lonf-term parenteral nutition
Ševela, Stanislav ; Novák, František (advisor) ; Cahová, Monika (referee) ; Lahoda Brodská, Helena (referee)
The combination of intestinal failure and parenteral nutrition is a condition associated with mild chronic inflammation and organ injury, the most significant of which is hepatic injury. This crossover-controlled trial investigated the effects of different intravenous lipid emulsions (IVLE) enriched with increased doses of omega-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) in patients on home parenteral nutrition (HPNP) for chronic intestinal failure. Twelve patients were consecutively given three different IVLEs, with an FO emulsion added after each IVLE. The study also included twelve paired healthy controls for comparison. The aim of this study was to investigate how long-term administration of these IVLEs affected primarily the erythrocyte and plasma fatty acid (FA) spectrum, as well as the inflammatory response, antioxidant status, markers of liver function and bile acid spectrum in HPNP, and how these changes differed from healthy subjects. We demonstrated successful incorporation of n-3 PUFA into erythrocyte phospholipids and corresponding changes in the plasma FA spectrum, characterized in particular by significant increases in n-3 versus n-6 PUFA, with a decrease in the n-6/n-3 PUFA ratio. We also found a more prolonged effect on these changes with high dose FO...
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Some aspects of molecular mechanisms of xenobiotics' hepatotoxicity and hepatoprotection : Modulatory roles of natural polyphenols
Lekic, Nataša ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Brůha, Radan (referee)
Background & Aims: Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. The aim of this work is to find early signal markers of drug-induced injury of the liver by focusing on select antioxidant/oxidant and apoptotic genes. As well, to address the relationship between conventional liver dysfunction markers and the measured mRNA and protein expressions in the D-galactosamine/lipopolysaccharide and tert-butylhydroperoxide hepatotoxicity models. Furthermore, potential hepatoprotective capabilities of antioxidant polyphenols quercetin and curcumin were evaluated in relation to its modulation of the oxidative stress and apoptotic parameters in the given xenobiotic hepatotoxicity models. Methods: Biochemical markers testing the hepatic function included aminotransferases (ALT, AST) and bilirubin. Measurements of TBARS and conjugated dienes were used to assess lipoperoxidation. Plasma levels of catalase and reduced glutathione were used as indicators of the oxidative status of the cell. Real time PCR was used to analyse the mRNA expressions of the inducible nitric oxide synthase (NOS-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD-1), glutathione peroxidase (Gpx-1), caspase 3 (Casp3), BH3 interacting domain death agonist (Bid) and Bcl-2...
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Some aspects of molecular mechanisms of xenobiotics' hepatotoxicity and hepatoprotection : Modulatory roles of natural polyphenols
Lekic, Nataša ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Brůha, Radan (referee)
Background & Aims: Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. The aim of this work is to find early signal markers of drug-induced injury of the liver by focusing on select antioxidant/oxidant and apoptotic genes. As well, to address the relationship between conventional liver dysfunction markers and the measured mRNA and protein expressions in the D-galactosamine/lipopolysaccharide and tert-butylhydroperoxide hepatotoxicity models. Furthermore, potential hepatoprotective capabilities of antioxidant polyphenols quercetin and curcumin were evaluated in relation to its modulation of the oxidative stress and apoptotic parameters in the given xenobiotic hepatotoxicity models. Methods: Biochemical markers testing the hepatic function included aminotransferases (ALT, AST) and bilirubin. Measurements of TBARS and conjugated dienes were used to assess lipoperoxidation. Plasma levels of catalase and reduced glutathione were used as indicators of the oxidative status of the cell. Real time PCR was used to analyse the mRNA expressions of the inducible nitric oxide synthase (NOS-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD-1), glutathione peroxidase (Gpx-1), caspase 3 (Casp3), BH3 interacting domain death agonist (Bid) and Bcl-2...
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