D-Galactosamine/Lipopolysaccharide (D-GalN/LPS) is a well known model of hepatotoxicity that closely resembles acute liver failure (ALF) seen clinically. The role of sirtuin 1 in this model has not yet been documented. However, there have been a number of studies about the cytoprotective effects of resveratrol, a SIRT1 activator, in the liver. This study was aimed at elucidating the roles of SIRT1 protein expression or catalytic activity in DGalN/ LPS model of hepatotoxicity. ALF was induced in male Wistar rats by intraperitoneal injection of D-GalN and LPS. Some groups of animals were pretreated with resveratrol and/or EX-527 (SIRT1 inhibitor). The effects of these treatments were evaluated by biochemical and Western blot studies. D-GalN/LPS treatment was able to induce hepatotoxicity and significantly increase all markers of liver damage and lipid peroxidation. A dramatic decrease of SIRT1 levels in response to D-GalN/LPS treatment was also documented. Resveratrol pretreatment attenuated D-GalN/LPS-induced hepatotoxicity. EX-527 blocked the cytoprotective effects of resveratrol. However, both resveratrol and EX-527 pretreatments did not exhibit any significant effect on SIRT1 protein expression. Collectively, these results suggest that downregulation of SIRT1 expression is involved in the cytotoxic effects of D-GalN/LPS model and SIRT1 activity contributes to the cytoprotective effects of resveratrol in the liver., M. K. Kemelo, L. Wojnarová, N. Kutinová Canová, H. Farghali., and Obsahuje bibliografii
Considering the preexisting influence of the process of natural aging on antioxidant enzymes activity and the level of lipid peroxidation, the age of the rats at which D-galactose (D-gal) treatment is started could strongly impact the development of D-gal induced senescence. To eval uate this, we subjected 1, 3 and 15 months old rats to D-gal treatment in parallel with having appropriate placebos (0.9 % saline). Our results showed elevated glutathione peroxidase (GPx) acti vity and no significant changes in superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) activity or malondialdehyde (MDA) levels in relation to natural aging. In mature and aged senescent livers we observed positive correlation between increased ratio R=SOD/(GPx+CAT) and increased MDA concentration. MDA levels seemed to correlate positively with the age of the animals at which D-gal treatment had started. In the case of 3 and 15 months old rats there was D-gal induced decrease in SOD and GR activity, but this effect of the treatment was not observed in 1 month old rats. Our results imply that the changes in the antioxidant enzyme activities are not only under the influence of the D-gal overload, but also depend on the developmental stage of the rats. According to our resu lts, with regard to enzymatic antioxidant capacity and the level of lipid peroxidation, the best age for induction of senescence is somewhere after the third month., N. Hadzi-Petrushev, V. Stojkovski, D. Mitrov, M. Mladenov., and Obsahuje bibliografii
CZ Praha Národní knihovna ČR 9 H 269 adl.2, CZ Praha Královská kanonie premonstrátů na Strahově - Strahovská knihovna AA XV 42 n.6, CZ Olomouc Vědecká knihovna v Olomouci 16.831, Pragæ in officina typographica Georgij Melantrichi ab Auentino. Anno Domini, 1560., and BCBT30947
Index, Na přídeští je fialové hranaté razítko Ústav pro zdravotnickou dokumentaci, na rubu titulního listu červené hranaté razítko Státní ústav pro zdravotnickou dokumentační a knihovnickou službu, Jedná se o tisk na ručním papíře, svázaný do celopergamenové vazby s lepenkovými deskami Kniha byla v roce 2004 restaurována K Opatovou Kniha je uložena v ochranném pouzdře z nekyselé lepenky, Restaurování 2004 Desinfekce, oprava oprava původní vazby, and Digitalizace 2004 AiP Beroun