Inhibition of TNF-α protects against hepatic ischemia-reperfusion injury in rats via NF-κB dependent pathway.
Hepatic ischemia-reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-α) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab-treated groups showed a significantly lower extent and severity of liver injury. This is attributed to (1) a decrease in oxidative stress markers, (2) reduction of the expression of TNF-α, TNF-α type-1 receptors, and nuclear factor kappa B (NF-κB). Thus TNF-α inhibition may be one of the therapeutic interventions to overcome the deleterious effects of I/R on liver via reduction of oxidative stress and inhibition of inflammatory cascade.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt. mfabdelaziz@zu.edu.eg
Mona F
MF
Mahmoud
Shimaa M
SM
El Shazly
Waleed
W
Barakat
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D000069285:Infliximab; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000069285:Infliximab; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D010431:Pentoxifylline