Recombinant human erythropoietin protects the liver from hepatic ischemia-reperfusion injury in the rat.
Recently, erythropoietin was shown to have both hematopoietic as well as tissue-protective properties. Erythropoietin (EPO) had a protective effect in animal models of cerebral ischemia, mechanical trauma of the nervous system, myocardial infarction, and ischemia-reperfusion (I/R) injury of the kidney. It is not known whether EPO protects the liver against I/R injury. Using a rat model of liver I/R injury, we aimed to determine the effect of the administration of human recombinant erythropoietin (rhEPO) on liver injury. Rats were subjected to 30 min of liver ischemia followed by 2 h of reperfusion. When compared with the sham-operated rats, I/R resulted in significant rises in the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase, tissue lipid peroxidation, caspase-3 activity and altered histology. Administration of rhEPO 5 min before ischemia was able to reduce the biochemical evidence of liver injury; however, this protection was not evident when rhEPO was administered 5 min before reperfusion. Mechanistically, early administration of rhEPO was able to reduce the oxidative stress and caspase-3 activation, suggesting the subsequent reduction of apoptosis. This study provides the first evidence that rhEPO causes a substantial reduction of the liver injury induced by I/R in the rat.
Sepodes
Bruno
B
Faculty of Pharmacy, Unit of Pharmacology and Pharmacotoxicology, University of Lisbon, Av. Forças Armadas, Lisbon, Portugal.
Maio
Rui
R
Pinto
Rui
R
Sharples
Edward
E
Oliveira
Pedro
P
McDonald
Michelle
M
Yaqoob
Muhammad
M
Thiemermann
Christoph
C
Mota-Filipe
Helder
H
D000818:Animals; D001671:Biochemistry / Q000379:methods; D020169:Caspases / Q000378:metabolism; D004921:Erythropoietin / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007511:Ischemia / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D020169:Caspases