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
Oxidative stress and mitochondrial dysfunction play an important role in the pathogenesis of nonalcoholic fatty liver disease and toxic liver injury. The present study was designed to evaluate the effect of exogenous inducer of oxidative stress (tert-butyl hydroperoxide, tBHP) on nonfatty and steatotic hepatocytes isolated from the liver of rats fed by standard and high-fat diet, respectively. In control steatotic hepatocytes, we found higher generation of ROS, increased lipoperoxidation, an altered redox state of glutathione, and decreased ADP-stimulated respiration using NADH-linked substrates, as compared to intact lean hepatocytes. Fatty hepatocytes exposed to tBHP exert more severe damage, lower reduced glutathione to total glutathione ratio, and higher formation of ROS and production of malondialdehyde and are more susceptible to tBHP-induced decrease in mitochondrial membrane potential. Respiratory control ratio of complex I was significantly reduced by tBHP in both lean and steatotic hepatocytes, but reduction in NADH-dependent state 3 respiration was more severe in fatty cells. In summary, our results collectively indicate that steatotic rat hepatocytes occur under conditions of enhanced oxidative stress and are more sensitive to the exogenous source of oxidative injury. This confirms the hypothesis of steatosis being the first hit sensitizing hepatocytes to further damage.
- MeSH
- dieta s vysokým obsahem tuků MeSH
- glutathion metabolismus MeSH
- hepatocyty účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- malondialdehyd metabolismus MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- nealkoholová steatóza jater metabolismus patologie MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- terc-butylhydroperoxid toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fatty liver disease associated with obesity is an important medical problem and the mechanisms for lipid accumulation in hepatocytes are not fully elucidated yet. Recent findings indicate that mitochondria play an important role in this process. Our data on hepatocytes in which mitochondria are in contact with other cytosolic structures important for their function, extend observations obtained on isolated mitochondria and confirm inhibition of Complex I activity in hepatocytes isolated from rats fed by high fat diet (HFD) compared with controls fed by standard diet (STD). Furthermore we have found that HFD-hepatocytes are more sensitive to the peroxidative stress because under these conditions also Complex II activity is disturbed. Therefore in HFD animals decrease of Complex I activity cannot be compensated by Complex II substrates as in STD hepatocytes. Our data thus indicates that combination of HFD and peroxidative stress potentiates HFD damaging effect of mitochondria because both branches of the respiratory chain (NADH- and flavoprotein-dependent) are disturbed.
- MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- hepatocyty fyziologie MeSH
- jaterní mitochondrie fyziologie MeSH
- krysa rodu rattus MeSH
- oxidační stres fyziologie MeSH
- potkani Wistar 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
S-adenosylmethionine (SAMe) is a key metabolite regulating growth, differentiation and death of hepatocytes. Experimentally, exogenous SAMe has been documented to attenuate hepatocarcinogenesis. The aim of our study was to evaluate the effect of SAMe on proliferation of hepatocytes that are not cancerously transformed. Partial 2/3 hepatectomy (PH) was performed in rats, control animals underwent laparotomy. SAMe was injected immediately after the surgery and then at 24 h intervals for two days at 10 or 40 mg/kg. The animals were sacrificed 24, 48 and 72 h after operation and the intensity of liver regeneration was evaluated. SAMe treatment at 10 mg/kg was associated with decrease in the synthesis of liver DNA 48 h after PH, however, it was not reflected in DNA content. SAMe treatment at 40 mg/kg led to the reduction of DNA synthesis 72 h after PH followed by the diminution of DNA content. The results have documented the inhibition of the liver regeneration by SAMe that may be mediated by the suppression of liver fat accumulation. Cell GSH level correlating with the growth rate was not affected by SAMe. Prevention from the decrease in the intracellular content of SAMe, as a factor attenuating regeneration remains to be verified.
- MeSH
- hepatektomie MeSH
- játra účinky léků patologie chirurgie MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- regenerace jater účinky léků fyziologie MeSH
- S-adenosylmethionin aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Liver regeneration in mammals is a unique phenomenon attracting scientific interest for decades. It is a valuable model for basic biology research of cell cycle control as well as for clinically oriented studies of wide and heterogeneous group of liver diseases. This article provides a concise review of current knowledge about the liver regeneration, focusing mainly on rat partial hepatectomy model. The three main recognized phases of the regenerative response are described. The article also summarizes history of molecular biology approaches to the topic and finally comments on obstacles in interpreting the data obtained from large scale microarray-based gene expression analyses.
- MeSH
- exprese genu MeSH
- financování organizované MeSH
- játra metabolismus MeSH
- lidé MeSH
- regenerace jater fyziologie genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
