Low-dose erythropoietin aggravates endotoxin-induced organ damage in conscious rats.
Endotoxin shock can induce the production of several inflammatory mediators such as TNF-alpha, IL-6, and IL-1beta, leading to multiple organ dysfunction and death. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R), expressed in a wide variety of non-hematopoietic tissues, to induce a range of pleiotropic cytoprotective actions. We investigated the effects of low doses of EPO (300U/kg, intravenous administration) on the physiopathology and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Escherichia coli lipopolysaccharide (20mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48h after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured at 0, 1, 3, 6, 9, 12, 18, 24, and 48h after sepsis. Serum TNF-alpha, IL-6, and IL-1beta level was measured at 1h after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, TNF-alpha, IL-6, IL-1beta levels, and HR, while it decreased MAP. EPO further increased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, and CPK), inflammatory biomarkers (TNF-alpha, IL-6, and IL-1beta) and did not affect MAP and HR after LPS. EPO disserved endotoxin shock-induced liver, kidney, lung, and small intestine damage in conscious rats. In conclusion, pre-treatment with low doses of EPO increased the release of TNF-alpha, IL-6, and IL-1beta, along with aggravating endotoxin shock-induced markers of organ injury in conscious rats.
Wu
Wen-Tien
WT
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Hu
Tsung-Ming
TM
Lin
Nien-Tsung
NT
Subeq
Yi-Maun
YM
Lee
Ru-Ping
RP
Hsu
Bang-Gee
BG
D000818:Animals; D004731:Endotoxins / Q000009:adverse effects / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D012772:Shock, Septic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004731:Endotoxins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin