Hepatoprotective effects of erythropoietin on D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice.
Fulminant hepatic failure is a severe clinical syndrome associated with a high rate of patient mortality. Recent studies have shown that in addition to its hematopoietic effect, erythropoietin (EPO) has multiple protective effects and exhibits antiapoptotic, antioxidant and anti-inflammatory activities. The present study aimed to determine the hepatoprotective effect of EPO and to elucidate the underlying mechanisms using a D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced model of acute liver injury. Experimental groups of mice were administered with various doses of EPO (1,000, 3,000 or 10,000 U/kg, intraperitoneal) once per day for 3 days, prior to injection with D-GalN (700 mg/kg)/LPS (10 µg/kg). Mice were sacrificed 8 h after treatment with D‑GalN/LPS. Liver function and histopathology, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH‑Px) activities and EPO receptor (EPOR) and phosphatidylinositol 3-kinase (PI3K) mRNA expression were evaluated. D-GalN/LPS administration markedly induced liver injury, as evidenced by elevated levels of serum aminotransferases, as well as histopathological changes. Compared with the D-GalN/LPS group, pretreatment with EPO significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase and MDA, and increased the activities of SOD and GSH-Px. Furthermore, the protective effects of EPO were paralleled by an upregulation in the mRNA expression of EPOR and PI3K. These data suggest that EPO can ameliorate D-GalN/LPS-induced acute liver injury by reducing oxidative stress and upregulating the mRNA expression of EPOR and PI3K.
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Xue-Fei
XF
Yang
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Yi
Y
He
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Hai-Yuan
HY
Li
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Xin
X
Liu
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Huan
H
Chen
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Jian-Bang
JB
Liu
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Wen-Jun
WJ
Ji
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Bing
B
Wang
Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Li-Na
LN
Chen
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004195:Disease Models, Animal; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D008070:Lipopolysaccharides; D020011:Protective Agents; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde; D000068817:Epoetin Alfa; D005688:Galactosamine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D058539:Phosphatidylinositol 3-Kinase