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Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury.
Hum Exp Toxicol. 2021 Aug; 40(8):1362-1373.HE

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, 195495Al-Azhar University, Assiut, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, 195495Al-Azhar University, Assiut, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, 195495Al-Azhar University, Assiut, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33655798

Citation

Hassan, Mohamed Ia, et al. "Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS Pathways in the Impact of Carvedilol Against Hepatic Ischemia Reperfusion Injury." Human & Experimental Toxicology, vol. 40, no. 8, 2021, pp. 1362-1373.
Hassan MI, Ali FE, Shalkami AS. Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury. Hum Exp Toxicol. 2021;40(8):1362-1373.
Hassan, M. I., Ali, F. E., & Shalkami, A. S. (2021). Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury. Human & Experimental Toxicology, 40(8), 1362-1373. https://doi.org/10.1177/0960327121999442
Hassan MI, Ali FE, Shalkami AS. Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS Pathways in the Impact of Carvedilol Against Hepatic Ischemia Reperfusion Injury. Hum Exp Toxicol. 2021;40(8):1362-1373. PubMed PMID: 33655798.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury. AU - Hassan,Mohamed Ia, AU - Ali,Fares Em, AU - Shalkami,Abdel-Gawad S, Y1 - 2021/03/03/ PY - 2021/3/4/pubmed PY - 2022/1/12/medline PY - 2021/3/3/entrez KW - Carvedilol KW - NOS KW - ROS KW - TNF-α KW - hepatic ischemia/reperfusion KW - inflammation SP - 1362 EP - 1373 JF - Human & experimental toxicology JO - Hum Exp Toxicol VL - 40 IS - 8 N2 - 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. SN - 1477-0903 UR - https://www.unboundmedicine.com/medline/citation/33655798/Role_of_TLR_4/IL_6/TNF_α_COX_II_and_eNOS/iNOS_pathways_in_the_impact_of_carvedilol_against_hepatic_ischemia_reperfusion_injury_ L2 - https://journals.sagepub.com/doi/10.1177/0960327121999442?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -