scholarly journals Sirtuin-Activating Compounds (STACs) Alleviate D-Galactosamine/Lipopolysaccharide-Induced Hepatotoxicity in Rats: Involvement of Sirtuin 1 and Heme Oxygenase 1

2017 ◽  
pp. 497-505 ◽  
Author(s):  
M. K. KEMELO ◽  
N. KUTINOVÁ CANOVÁ ◽  
A. HORINEK ◽  
H. FARGHALI
Keyword(s):  
Heme Oxygenase ◽  
Sirtuin 1 ◽  
Heme Oxygenase 1 ◽  
Conjugated Diene ◽  
Sirt1 Expression ◽  
Natural Polyphenol ◽  
Biochemical Studies ◽  
Male Wistar Rats ◽  
Lps Treatment ◽  
Sirt1 Activator

Sirtuin activating compounds (STACs) attenuate various type of liver insults through mechanisms which are not fully understood. In the present study, we investigated the ameliorative potential of quercetin (natural polyphenol) and SRT1720 (synthetic SIRT1 activator) against D-galactosamine/lipopolysaccharide-induced hepatotoxicity (an experimental model of acute liver failure). Moreover, we compared and contrasted the roles of stress responsive enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) in hepatoprotection/ hepatotoxicity. Liver injury was induced in male Wistar rats by intraperitoneal injection of D-galactosamine (400 mg/kg) and lipopolysaccharide (10 µg/kg). Some animals were pretreated with quercetin (50 mg/kg i.p.) or SRT1720 (5 mg/kg i.p.). Twenty-four hours later, the effects of these treatments were evaluated by biochemical studies and Western blot. D-GalN/LPS treatment upregulated HO-1 expression, downregulated SIRT1 expression, decreased AST:ALT ratio and markedly increased bilirubin, catalase and conjugated diene levels. Pretreatment of D-GalN/LPS rats with either quercetin or SRT1720 returned SIRT1 expression, HO-1 expression and all the aforementioned markers towards normal. Collectively, these findings suggest that elevated HO-1 and low SIRT1 expressions are involved in the pathogenesis of D-GalN/LPS-induced hepatotoxicity. Drugs that downregulate HO-1 and/or upregulate SIRT1 seem to have antihepatotoxic effects and need further exploration.

scholarly journals D-Galactosamine/Lipopolysaccharide-Induced Hepatotoxicity Downregulates Sirtuin 1 in Rat Liver: Role of Sirtuin 1 Modulation in Hepatoprotection

2014 ◽  
pp. 615-623
Author(s):  
M. K. KEMELO ◽  
L. WOJNAROVÁ ◽  
N. KUTINOVÁ CANOVÁ ◽  
H. FARGHALI
Keyword(s):  
Protein Expression ◽  
Wistar Rats ◽  
Sirtuin 1 ◽  
Dramatic Decrease ◽  
Cytotoxic Effects ◽  
Male Wistar Rats ◽  
Sirt1 Inhibitor ◽  
Lps Treatment ◽  
Sirt1 Activator

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 D-GalN/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.

Hypoxia Inducible Factor-1 Alpha Correlates the Expression of Heme Oxygenase 1 Gene in Pulmonary Arteries of Rat with Hypoxia-induced Pulmonary Hypertension

2004 ◽  
Vol 36 (2) ◽  
pp. 133-140 ◽  
Author(s):  
Qi-Fang Li ◽  
Ai-Guo Dai
Keyword(s):  
Pulmonary Hypertension ◽  
Heme Oxygenase ◽  
Hypoxia Inducible Factor ◽  
Pulmonary Arteries ◽  
Heme Oxygenase 1 ◽  
Hypoxia Inducible Factor 1 ◽  
Mean Pulmonary Arterial Pressure ◽  
Male Wistar Rats ◽  
Pulmonary Arterial ◽  
Tunica Intima

Abstract To test the hypothesis that hypoxia inducible factor-1 alpha (HIF-1α) up-regulated the expression of heme oxygenase-1 (HO-1) gene in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension, 8 male Wistar rats in each of 5 groups were exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index were measured. Lungs were inflation fixed for immunohistochemistry, in situ hybridization; frozen for later measurement of HO-1 enzyme activity. mPAP increased significantly after 7 d of hypoxia [(18.4 ± 0.4) mmHg, P<0.05], reaching its peak after 14 d of hypoxia, then remained stable. Pulmonary artery remodeling became to develop significantly after 14 d of hypoxia. HIF-1α protein in control was poorly positive (0.05 ± 0.01), but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, the levels of HIF-1α protein were markedly up-regulated after 3 d and 7 d of hypoxia (0.20 ± 0.02; 0.22 ± 0.02, P<0.05), then declined after 14 d and 21 d of hypoxia. HIF-1α mRNA staining was poorly positive in control, hypoxia for 3 and 7 d, but enhanced significantly after 14 d of hypoxia (0.20 ± 0.02, P<0.05), then remained stable. HO-1 protein increased after 7 d of hypoxia (0.10 ± 0.01, P<0.05), reaching its peak after 14 d of hypoxia (0.21 ± 0.02, P<0.05), then remained stable. HO-1 mRNA increased after 3 d of hypoxia, reaching its peak after 7 d of hypoxia (0.17 ± 0.01, P<0.05), then declined. Linear correlation analysis showed that HIF-1α mRNA, HO-1 protein and mPAP were associated with pulmonary remodeling. HIF-1α protein (tunica intima) was conversely correlated with HIF-1α mRNA (r=0.921, P<0.01), HO-1 protein was conversely correlated with HIF-1α protein (tunica intima) (r=0.821, P<0.01). HIF-1α and HO-1 were both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rat. Hypoxia inducible factor-1 alpha correlated the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.

scholarly journals Heme oxygenase-1 regulates sirtuin-1-autophagy pathway in liver transplantation: From mouse to human

2017 ◽  
Vol 18 (5) ◽  
pp. 1110-1121 ◽  
Author(s):  
Kojiro Nakamura ◽  
Shoichi Kageyama ◽  
Shi Yue ◽  
Jing Huang ◽  
Takehiro Fujii ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Heme Oxygenase ◽  
Sirtuin 1 ◽  
Heme Oxygenase 1 ◽  
Autophagy Pathway

scholarly journals Effect of a heme oxygenase-1 inducer on NADPH oxidase expression in alcohol-induced liver injury in male Wistar rats

2017 ◽  
Vol 16 (5) ◽  
pp. 1039 ◽  
Author(s):  
Phanit Koomhin ◽  
Chuchard Punsawad ◽  
Prasit Suwannalert ◽  
Sarawoot Palipoch
Keyword(s):  
Liver Injury ◽  
Nadph Oxidase ◽  
Heme Oxygenase ◽  
Wistar Rats ◽  
Heme Oxygenase 1 ◽  
Male Wistar Rats
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