Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury

2021 ◽  
pp. 096032712199944
Author(s):  
Mohamed IA Hassan ◽  
Fares EM Ali ◽  
Abdel-Gawad S Shalkami
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Liver Enzymes ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Aim: Hepatic ischemia/reperfusion (I/R) injury is a syndrome involved in allograft dysfunction. This work aimed to elucidate carvedilol (CAR) role in hepatic I/R injury. Methods: Male rats were allocated to Sham group, CAR group, I/R group and CAR plus I/R group. Rats subjected to hepatic ischemia for 30 minutes then reperfused for 60 minutes. Oxidative stress markers, inflammatory cytokines and nitric oxide synthases were measured in hepatic tissues. Results: Hepatocyte injury following I/R was confirmed by a marked increase in liver enzymes. Also, hepatic I/R increased the contents of malondialdehyde however decreased glutathione contents and activities of antioxidant enzymes. Furthermore, hepatic I/R caused elevation of toll-like receptor-4 (TLR-4) expression and inflammatory mediators levels such as tumor necrosis factor-α, interleukin-6 and cyclooxygenase-II. Hepatic I/R caused down-regulation of endothelial nitric oxide synthase and upregulation of inducible nitric oxide synthase expressions. CAR treatment before hepatic I/R resulted in the restoration of liver enzymes. Administration of CAR caused a significant correction of oxidative stress and inflammation markers as well as modulates the expression of endothelial and inducible nitric oxide synthase. Conclusions: CAR protects liver from I/R injury through reduction of the oxidative stress and inflammation, and modulates endothelial and inducible nitric oxide synthase expressions.

scholarly journals Dynamics of Nitrotyrosine Formation and Decay in Rat Brain during Focal Ischemia-Reperfusion

1999 ◽  
Vol 19 (6) ◽  
pp. 667-672 ◽  
Author(s):  
Shunya Takizawa ◽  
Naoto Fukuyama ◽  
Hisayuki Hirabayashi ◽  
Hiroe Nakazawa ◽  
Yukito Shinohara
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Rat Brain ◽  
Inducible Nitric Oxide Synthase ◽  
Time Window ◽  
Ischemia Reperfusion ◽  
Late Phase ◽  
Focal Ischemia ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The purpose of this study was to establish the dynamics of nitrotyrosine (NO2-Tyr) formation and decay during the rise of NO2-Tyr in rat brain subjected to 2-hour focal ischemia-reperfusion, and to evaluate the role of inducible nitric oxide synthase in the rise. The authors first determined the half life of NO2-Tyr in rat brain at 24 hours after the start of reperfusion by blocking NO2-Tyr formation with NG-monomethyl-l-arginine and after the decay of NO2-Tyr by means of a hydrolysis/HPLC procedure. The values obtained were approximately 2 hours in both peri-infarct and core-of-infarct regions. Using the same hydrolysis/HPLC procedure, the ratio of nitrotyrosine to tyrosine from the 2-hour occlusion to as much as 72 hours after the start of reperfusion was measured in the presence and absence of aminoguanidine (100 mg/kg intraperitoneally twice a day). In the absence of aminoguanidine, the ratio of NO2-Tyr in the peri-infarct and core-of-infarct regions reached 0.95% ± 0.34% and 0.52% ± 0.34%, respectively, at 1 hour after the start of reperfusion, The elevated levels persisted until 48 hours, then declined, The peri-infarct region showed the highest percent NO2-Tyr level, followed by the core of infarct, then the caudoputamen, Aminoguanidine significantly reduced NO2-Tyr formation (up to 90% inhibition) during 24 to 48 hours, The authors conclude that inducible nitric oxide synthase is predominantly responsible for NO2-Tyr formation, at least in the late phase of reperfusion, These results have important implications for the therapeutic time window and choice of nitric oxide synthase inhibitors in patients with cerebral infarction.

The role of differnt isoforms of nitric oxide synthase (NOS) in hepatic ischemia-reperfusion infjury in mice

2001 ◽  
Vol 120 (5) ◽  
pp. A549
Author(s):  
Shigeyuki Kawachi ◽  
Motohide Shimazu ◽  
Masaki Kitajima ◽  
Matthew B. Grisham
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Oxide Synthase
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