- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
AIM: The aim of our study was to assess whether simple steatosis impairs liver regeneration after partial hepatectomy (PHx) in rats. METHODS: Male Sprague-Dawley rats were fed a standard diet (ST-1, 10% kcal fat) and high-fat diet (HFD, 71% kcal fat) for 6 weeks. Then the rats were submitted to 2/3 PHx and animals were sacrificed 24, 48 or 72 h after PHx. Serum biochemistry, respiration of mitochondria in liver homogenate, hepatic oxidative stress markers, selected cytokines and DNA content were measured, and histopathological samples were prepared. Liver regeneration was evaluated by incorporation of bromodeoxyuridine (BrdU) to hepatocyte DNA. RESULTS: HFD induced simple microvesicular liver steatosis. PHx caused elevation of serum markers of liver injury in both groups; however, an increase in these parameters was delayed in HFD group. Hepatic content of reduced glutathione was significantly increased in both groups after PHx. There were no significant changes in activities of respiratory complexes I and II (state 3). Relative and absolute liver weights, total DNA content, and DNA synthesis exerted very similar changes in both ST-1 and HFD groups after PHx. CONCLUSION: PHx-induced regeneration of the rat liver with simple steatosis was not significantly affected when compared to the lean liver.
- MeSH
- hepatektomie * MeSH
- jaterní mitochondrie patologie fyziologie MeSH
- jaterní testy MeSH
- játra patologie patofyziologie MeSH
- krysa rodu rattus MeSH
- potkani Sprague-Dawley MeSH
- regenerace jater fyziologie MeSH
- ztučnělá játra patologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Anthracycline anticancer drugs (e.g., doxorubicin or daunorubicin) can induce chronic cardiotoxicity and heart failure (HF), both of which are believed to be based on oxidative injury and mitochondrial damage. In this study, molecular and functional changes induced by chronic anthracycline treatment with progression into HF in post-treatment follow-up were analyzed with special emphasis on nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) pathways. Chronic cardiotoxicity was induced in rabbits with daunorubicin (3 mg/kg, weekly for 10 weeks), and the animals were followed for another 10 weeks. Echocardiography revealed a significant drop in left ventricular (LV) systolic function during the treatment with marked progression to LV dilation and congestive HF in the follow-up. Although daunorubicin-induced LV lipoperoxidation was found, it was only loosely associated with cardiac performance. Furthermore, although LV oxidized glutathione content was increased, the oxidized-to-reduced glutathione ratio itself remained unchanged. Neither Nrf2, the master regulator of antioxidant response, nor the majority of its target genes showed up-regulation in the study. However, down-regulation of manganese superoxide dismutase and NAD(P)H dehydrogenase [quinone] 1 were observed together with heme oxygenase 1 up-regulation. Although marked perturbations in mitochondrial functions were found, no induction of PGC1α-controlled mitochondrial biogenesis pathway was revealed. Instead, especially in the post-treatment period, an impaired regulation of this pathway was observed along with down-regulation of the expression of mitochondrial genes. These results imply that global oxidative stress need not be a factor responsible for the development of anthracycline-induced HF, whereas suppression of mitochondrial biogenesis might be involved.
- MeSH
- antibiotika antitumorózní toxicita MeSH
- antracykliny toxicita MeSH
- buněčné jádro účinky léků metabolismus MeSH
- daunomycin farmakologie MeSH
- echokardiografie MeSH
- faktor 2 související s NF-E2 biosyntéza MeSH
- funkční vyšetření srdce MeSH
- glutathion metabolismus MeSH
- králíci MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- myokard patologie MeSH
- nemoci srdce chemicky indukované metabolismus MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- přežití MeSH
- srdeční komory účinky léků metabolismus MeSH
- srdeční mitochondrie účinky léků metabolismus MeSH
- transkripční faktory metabolismus MeSH
- troponin T metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antiinflammatory effect of statins mediated by the reduction of cytokine IL-6 in hepatocytes have been reported. Contrary to beneficial effect, statins can increase susceptibility to mitochondrial dysfunction. Extrahepatic biliary obstruction is associated with oxidative stress, pro-inflammatory response and hepatocyte mitochondrial dysfunction. The aim of our study was to verify the effect of fluvastatin on cholestatic liver injury. Cholestasis was induced in Wistar rats by bile duct ligation. Fluvastatin (1 or 5 mg/kg) was administered after surgery and then daily for 7 days. The dose of 5 mg/kg led to the deterioration of hepatocellular injury. Despite lower production of IL-6, decrease in GSH content, rise of TGFß and inhibition of respiratory complex I in mitochondria were determined. The mRNA expressions of canalicular transporter Mdr1b and basolateral transporter Mrp3 increased in cholestatic liver. Fluvastatin administration then led to the attenuation of this change. Analogously, mRNA expression of conjugative enzyme Ugt1a1 was diminished by fluvastatin administration to cholestatic rats. We can conclude that decrease in the antioxidative status and mitochondrial dysfunction could at least in part participate on the deteriorating effect of fluvastatin. Whether these processes can be a consequence of the alteration in metabolism and transport of potentially toxic substances remains to verify.
- MeSH
- alanintransaminasa krev účinky léků metabolismus MeSH
- alkalická fosfatasa krev účinky léků metabolismus MeSH
- aspartátaminotransferasy krev účinky léků metabolismus MeSH
- bilirubin krev metabolismus MeSH
- gama-glutamyltransferasa krev účinky léků metabolismus MeSH
- glukuronosyltransferasa účinky léků metabolismus MeSH
- glutathion účinky léků metabolismus MeSH
- indoly škodlivé účinky MeSH
- interleukin-6 metabolismus MeSH
- intrahepatální cholestáza farmakoterapie metabolismus MeSH
- játra účinky léků patologie MeSH
- krysa rodu rattus MeSH
- kyseliny mastné mononenasycené škodlivé účinky MeSH
- ligace MeSH
- messenger RNA účinky léků metabolismus MeSH
- potkani Wistar MeSH
- statiny škodlivé účinky MeSH
- transformující růstový faktor beta účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dieta škodlivé účinky MeSH
- dietní tuky škodlivé účinky MeSH
- financování organizované MeSH
- glutathion krev MeSH
- iontové kanály biosyntéza MeSH
- játra chemie MeSH
- krysa rodu rattus MeSH
- malondialdehyd metabolismus MeSH
- mitochondriální proteiny biosyntéza MeSH
- modely nemocí na zvířatech MeSH
- potkani Sprague-Dawley MeSH
- potkani Wistar MeSH
- triglyceridy krev MeSH
- ztučnělá játra etiologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
