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Administration of low doses of tumor necrosis factor-alpha protects rat liver from ischaemic damage and reperfusion injury.
J Physiol Pharmacol. 2010 Jun; 61(3):273-8.JP

Abstract

Liver ischaemia and reperfusion (IR) injury is a significant clinical problem. The aim of our study was to investigate the protective effect of tumor necrosis factor-alpha (TNF-alpha) on rat liver ischaemia-reperfusion injury. A TNF-alpha dose of 3 microg/kg body weight was injected into rats that had undergone partial (70%) ischaemia and reperfusion. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total blood antioxidant level (using the FRAP test), and the concentrations of TNF-alpha, myeloperoxidase (MPO) and malondialdehyde (MDA) in liver homogenates after 1, 6, and 72 hours of reperfusion were measured. It was demonstrated that, rats subjected to IR, the administration of small doses of TNF-alpha significantly reduced ALT and AST activities after 60- minute liver ischaemia and 1 or 6 hour of reperfusion. The strongest reductions in ALT and AST activities were seen after 1 hour of reperfusion (30% and 35%, respectively). Exogenous TNF-alpha reduced the release of this cytokine in all observed periods, with the greatest reduction observed after 1 hour of reperfusion. Decreases in MPO concentration (by 40-45% in all periods of observation), as a marker of hepatic neutrophil infiltration, and in MDA concentration, the end-product of lipid peroxidation (by 55-60% at all time points), accompanied the reduction of TNF-alpha release. The administration of TNF-alpha to the rats after IR did not alter total plasma antioxidant potential, as assayed by the FRAP test, after 1 hour of reperfusion; however, at the later times a marked increase (approximately 40-50%) occurred. We demonstrated that intraperitoneal injections of small doses of TNF-alpha protect rat livers from IR injury. The mechanism of this protection is related to reductions in the release of TNF-alpha during IR after injection of this cytokine, resulting in reductions in oxidative stress and inflammation during the later phase of reperfusion.

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Authors+Show Affiliations

Helewski KJ
Department of Histology and Embryology, Medical University of Silesia, Zabrze, Poland.
Kowalczyk-Ziomek GI
No affiliation info available
Czecior E
No affiliation info available
Swietochowska E
No affiliation info available
Wielkoszynski T
No affiliation info available
Czuba ZP
No affiliation info available
Szliszka E
No affiliation info available
Krol W
No affiliation info available

MeSH

Alanine TransaminaseAnimalsAspartate AminotransferasesLiverLiver DiseasesMaleMalondialdehydeOxidative StressPeroxidaseProtective AgentsRatsRats, WistarReperfusion InjuryTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20610856

Citation

Helewski, K J., et al. "Administration of Low Doses of Tumor Necrosis Factor-alpha Protects Rat Liver From Ischaemic Damage and Reperfusion Injury." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 61, no. 3, 2010, pp. 273-8.
Helewski KJ, Kowalczyk-Ziomek GI, Czecior E, et al. Administration of low doses of tumor necrosis factor-alpha protects rat liver from ischaemic damage and reperfusion injury. J Physiol Pharmacol. 2010;61(3):273-8.
Helewski, K. J., Kowalczyk-Ziomek, G. I., Czecior, E., Swietochowska, E., Wielkoszynski, T., Czuba, Z. P., Szliszka, E., & Krol, W. (2010). Administration of low doses of tumor necrosis factor-alpha protects rat liver from ischaemic damage and reperfusion injury. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 61(3), 273-8.
Helewski KJ, et al. Administration of Low Doses of Tumor Necrosis Factor-alpha Protects Rat Liver From Ischaemic Damage and Reperfusion Injury. J Physiol Pharmacol. 2010;61(3):273-8. PubMed PMID: 20610856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Administration of low doses of tumor necrosis factor-alpha protects rat liver from ischaemic damage and reperfusion injury. AU - Helewski,K J, AU - Kowalczyk-Ziomek,G I, AU - Czecior,E, AU - Swietochowska,E, AU - Wielkoszynski,T, AU - Czuba,Z P, AU - Szliszka,E, AU - Krol,W, PY - 2009/08/17/received PY - 2010/05/25/accepted PY - 2010/7/9/entrez PY - 2010/7/9/pubmed PY - 2010/10/22/medline SP - 273 EP - 8 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J Physiol Pharmacol VL - 61 IS - 3 N2 - Liver ischaemia and reperfusion (IR) injury is a significant clinical problem. The aim of our study was to investigate the protective effect of tumor necrosis factor-alpha (TNF-alpha) on rat liver ischaemia-reperfusion injury. A TNF-alpha dose of 3 microg/kg body weight was injected into rats that had undergone partial (70%) ischaemia and reperfusion. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total blood antioxidant level (using the FRAP test), and the concentrations of TNF-alpha, myeloperoxidase (MPO) and malondialdehyde (MDA) in liver homogenates after 1, 6, and 72 hours of reperfusion were measured. It was demonstrated that, rats subjected to IR, the administration of small doses of TNF-alpha significantly reduced ALT and AST activities after 60- minute liver ischaemia and 1 or 6 hour of reperfusion. The strongest reductions in ALT and AST activities were seen after 1 hour of reperfusion (30% and 35%, respectively). Exogenous TNF-alpha reduced the release of this cytokine in all observed periods, with the greatest reduction observed after 1 hour of reperfusion. Decreases in MPO concentration (by 40-45% in all periods of observation), as a marker of hepatic neutrophil infiltration, and in MDA concentration, the end-product of lipid peroxidation (by 55-60% at all time points), accompanied the reduction of TNF-alpha release. The administration of TNF-alpha to the rats after IR did not alter total plasma antioxidant potential, as assayed by the FRAP test, after 1 hour of reperfusion; however, at the later times a marked increase (approximately 40-50%) occurred. We demonstrated that intraperitoneal injections of small doses of TNF-alpha protect rat livers from IR injury. The mechanism of this protection is related to reductions in the release of TNF-alpha during IR after injection of this cytokine, resulting in reductions in oxidative stress and inflammation during the later phase of reperfusion. SN - 1899-1505 UR - https://www.unboundmedicine.com/medline/citation/20610856/Administration_of_low_doses_of_tumor_necrosis_factor_alpha_protects_rat_liver_from_ischaemic_damage_and_reperfusion_injury_ L2 - http://www.jpp.krakow.pl/journal/archive/06_10/pdf/273_06_10_article.pdf DB - PRIME DP - Unbound Medicine ER -