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.

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 Regulation of Biogenesis and Fusion/Fission Processes of Vascular Mitochondria In Aldosterone-Induced Hypertension

2018 ◽  
Vol 10 (1) ◽  
pp. 76-85
Author(s):  
Elena Olivares-Álvaro ◽  
María Belén Ruiz-Roso ◽  
Mercedes Klett-Mingo ◽  
Sandra Ballesteros ◽  
Ricardo Gredilla ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Protein Expression ◽  
Mitochondrial Biogenesis ◽  
Wistar Rats ◽  
Mitochondrial Alterations ◽  
Induced Hypertension ◽  
Male Wistar Rats ◽  
Vascular Oxidative Stress

Background:Aldosterone plays a key role in the development of endothelial dysfunction and hypertension. The regulation of biogenesis and fusion/fission processes of vascular mitochondria has not been examined in aldosterone-induced hypertension. Thereby, we sought to explore in greater depth the role of aldosterone in mitochondrial biogenesis and fusion/fission processes in hypertension and the associated increases in oxidative stress.Methods:Male Wistar rats received aldosterone (1mg/Kg/day) + 1% NaCl as drinking water for 3 weeks.Results:Systolic blood pressure was elevated (p<0.05) in aldosterone-treated rats. eNOS and p-eNOSSer1177protein expression was down regulated (p<0.05) and NADPH oxidase subunit p22phox expression was increased (p<0.05) in aldosterone-treated rats. Expression of mitochondrial biogenesis proteins SIRT1, PGC1α, PPARγ, and TFAM decreased (p<0.05) in aldosterone-treated rats. Protein expression of vascular DRP1, OMA1 and S-OPA1 up regulated (p<0.05) in aldosterone-treated rats. MFN1 and L-OPA1 (p<0.05) decreased in aldosterone-treated animals.Conclusion:The results showed that, in aldosterone-treated rats, hypertension is likely associated with increased oxidative stress in the aorta and with changes in the regulation of two key mitochondrial processes such as biogenesis and fusion/fission processes. The overall mitochondrial alterations observed in the study may play a role in aldosterone-derived vascular oxidative stress and hypertension.

P-OT002. Alcohol consumption alters the amygdalar protein expression of mTORC2 in male Wistar rats

2021 ◽  
Vol 132 (8) ◽  
pp. e123
Author(s):  
Athirah Hanim Binti Che Rahim ◽  
Mohd Helmy Mokhtar ◽  
Rashidi Mohamed Pakri ◽  
Isa Naina Mohamed ◽  
Jayakumar
Keyword(s):  
Alcohol Consumption ◽  
Protein Expression ◽  
Wistar Rats ◽  
Male Wistar Rats

scholarly journals Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

2020 ◽  
Vol 21 (13) ◽  
pp. 4815 ◽  
Author(s):  
Ekaterina P. Mochalova ◽  
Svetlana P. Belova ◽  
Tatiana Y. Kostrominova ◽  
Boris S. Shenkman ◽  
Tatiana L. Nemirovskaya
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Histone Deacetylases ◽  
Wistar Rats ◽  
Hindlimb Suspension ◽  
Skeletal Muscle Atrophy ◽  
E3 Ligases ◽  
Male Wistar Rats ◽  
Muscle Unloading

Unloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq). Male Wistar rats were divided into four groups (eight rats per group): nontreated control (C), three days of unloading/hindlimb suspension (HS) and three days HS with HDACs inhibitor LMK-235 (HSLMK) or Tq (HSTq). Treatment with LMK-235 diminished unloading-induced of MAFbx, myogenin (MYOG), ubiquitin and calpain-1 mRNA expression (p < 0.05). Tq administration had no effect on the expression of E3-ligases. The mRNA expression of MuRF1 and MAFbx was significantly increased in both HS and HSTq groups (1.5 and 4.0 folds, respectively; p < 0.05) when compared with the C group. It is concluded that during three days of muscle unloading: (1) the HDACs 4 and 5 participate in the regulation of MAFbx expression as well as the expression of MYOG, ubiquitin and calpain-1; (2) the inhibition of HDAC 4 has no effect on MAFbx expression. Therefore, HDAC 5 is perhaps more important for the regulation of MAFbx expression than HDAC 4.

scholarly journals The Beneficial Role of Anchomanes difformis in STZ-Induced Reproductive Dysfunction in Male Wistar Rats

2020 ◽  
Vol Volume 13 ◽  
pp. 4543-4560
Author(s):  
Toyin Dorcas Alabi ◽  
Charon de Villiers ◽  
Stefan S. du Plessis ◽  
Thomas K. Monsees ◽  
Nicole L. Brooks ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Reproductive Dysfunction ◽  
Beneficial Role ◽  
Male Wistar Rats

Role of paroxetine in interferon-α-induced immune and behavioural changes in male Wistar rats

2007 ◽  
Vol 21 (8) ◽  
pp. 843-850 ◽  
Author(s):  
A.M. Myint ◽  
S. O'Mahony ◽  
M. Kubera ◽  
Y.K. Kim ◽  
C. Kenny ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Interferon Α ◽  
Behavioural Changes ◽  
Male Wistar Rats

The role of microRNA in the response to cisplatin treatment

2012 ◽  
Vol 40 (4) ◽  
pp. 821-825 ◽  
Author(s):  
Ross M. Drayton
Keyword(s):  
Protein Expression ◽  
Cisplatin Resistance ◽  
Microrna Expression ◽  
Signalling Pathways ◽  
Cytotoxic Effects ◽  
Cellular Processes

Resistance to the cytotoxic effects of cisplatin can be mediated through changes in a wide variety of cellular processes and signalling pathways. The discovery of microRNAs as regulators of protein expression through the targeting of mRNA has led to a number of studies on the effect of cisplatin treatment on microRNA expression, and the ability of microRNAs to modulate cisplatin resistance.

Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases

2016 ◽  
Vol 244 ◽  
pp. 187-194 ◽  
Author(s):  
Nachimuthu Maithilikarpagaselvi ◽  
Magadi Gopalakrishna Sridhar ◽  
Rathinam Palamalai Swaminathan ◽  
Bobby Zachariah
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Inflammatory Response ◽  
Wistar Rats ◽  
Potential Role ◽  
High Fructose ◽  
Male Wistar Rats ◽  
Serine Kinases
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