The protective effect of recombinant human erythropoietin against cisplatin-induced renal and hepatic dysfunctions in Wistar rats

Mitomycin C (MMC) is one of the most effective chemotherapeutic drugs. However, the dose of MMC is greatly limited by its toxicity in normal tissues. Recombinant human erythropoietin (rhEPO), an erythropoietic hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against MMC-induced heart, liver, and renal dysfunction. Adult male Wistar rats were divided into six groups (with six animals each), namely control, rhEPO alone group, MMC alone group, and rhEPO + MMC group (pre-, co-, and posttreatment conditions). The results showed that MMC induced a marked cardiac, renal, and liver failure characterized by a significant decrease in body weight, organs weight, and organs ratio and a significant increase in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, and conjugated and total bilirubin levels in serum. Histological examination showed that MMC caused liver alterations. rhEPO treatment restored body weight, organs weight, and organs ratio as well as serum biochemical parameters and histological damage caused by MMC exposure.

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Exposure to Recombinant Human Erythropoietin Increases Survival of Red Blood Cells in Wistar Rats.

Blood ◽

10.1182/blood.v114.22.5087.5087 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5087-5087

Author(s):

Wojciech Krzyzanski ◽

Asfiha G Gebreegziabher ◽

Piotr Kawczak

Keyword(s):

Recombinant Human Erythropoietin ◽

Wistar Rats ◽

Survival Curve ◽

Reticuloendothelial System ◽

Erythroid Progenitor ◽

Human Erythropoietin ◽

Erythroid Progenitor Cells ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Abstract 5087 Purpose The primary goal of this study was to determine if exposure to recombinant human erythropoietin (rHuEPO) increases survival of RBCs in rats. A secondary objective was to test if rHuEPO prolongs survival of RBC by interaction with erythroid progenitor cells or by affecting cells of the reticuloendothelial system. Methods Normal male Wistar rats (337 ± 8 g) were divided into four groups (n=2). Animals in groups 0 and 1 were not treated whereas animals groups 2 and 3 received multiple doses of rHuEPO (Epogen, Amgen, CA) 450 IU/kg three times a week for two weeks via intravenous injections in the tail vein. Subsequently, blood samples (∼ 1-2 mL) were collected from all animals and labeled with water-soluble biotin as a tag for RBC. The biotinylated RBCs were injected back to animals according to the following pattern. Group 1 received blood from Group 2 and Group 2 from Group 1. Animals from Groups 0 and 3 were injected back with their own blood. Two days were allowed for a system equilibration. Next, blood samples (∼ 100 mL) were drawn weekly from each animal until the signal reached the limit of quantification. The biotinylated cells were detected by streptavidin conjugated to phycoerythin and analyzed by flow cytometry (FACSCalibur, Becton-Dickinson). The RBC absolute count was determined by a hematology analyzer (BC-2800 Vet, Mindray, China). The survival data were represented as the fraction of surviving cells. For quantification of RBC survival, the times necessary to reduce the size of the labeled sample by 25, 50, and 75% (T25, T50, and T75) were used. Results The mean survival curves for each group were compared to the control rats (Group 0). The survival curve for animals in Group 3 was distinctly higher that the survival curve for the control which was reflected by the T50 values of 31.5±1.6 and 13.6±0.1 days, respectively. This implies that the survival of RBCs is prolonged by the treatment with rHuEPO. If the effect of erythropoietin on RBC survival is mediated by its interaction with the erythroid progenitor cells, then an increase in the RBC survival in Group 1 is expected. This was somewhat confirmed by the survival curve for Group 1 that was above the control survival curve, however not to the extent of Group 3. Contrary, the survival curve for Group 2 overlapped with the control, supporting the hypothesis that the effect of rHuEPO on RBC survival is not mediated by its interaction with the reticuloendothelial system. The T50 values for Group 1 and 2 were 24.3±7.4 and 15.6±3.0 days, respectively. Conclusions The survival patterns of RBCs following two week long exposure to rHuEPO imply that their lifespan is prolonged when compared to control rats. Lack of an increase of RBC survival for Group 1 and a moderate increase of RBC survival for Group 2 support the endowment hypothesis that rHuEPO prolongs survival of RBCs possible by enhancing viability of the erythroid precursors. Disclosures No relevant conflicts of interest to declare.

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Induction of DNA fragmentation, chromosome aberrations and micronuclei by cisplatin in rat bone-marrow cells: Protective effect of recombinant human erythropoietin

Mutation Research/Genetic Toxicology and Environmental Mutagenesis ◽

10.1016/j.mrgentox.2012.05.011 ◽

2012 ◽

Vol 747 (2) ◽

pp. 202-206 ◽

Cited By ~ 16

Author(s):

Karima Rjiba-Touati ◽

Imen Ayed-Boussema ◽

Habib Skhiri ◽

Anis Belarbia ◽

Dorsaf Zellema ◽

...

Keyword(s):

Bone Marrow ◽

Protective Effect ◽

Dna Fragmentation ◽

Chromosome Aberrations ◽

Recombinant Human Erythropoietin ◽

Bone Marrow Cells ◽

Human Erythropoietin ◽

Rat Bone ◽

Marrow Cells

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Protective Effect of Recombinant Human Erythropoietin Against Cisplatin-Induced Oxidative Stress and Nephrotoxicity in Rat Kidney

International Journal of Toxicology ◽

10.1177/1091581811411931 ◽

2011 ◽

Cited By ~ 1

Author(s):

K. Rjiba-Touati ◽

I. Ayed-Boussema ◽

A. Belarbia ◽

A. Achour ◽

H. Bacha

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Recombinant Human Erythropoietin ◽

Rat Kidney ◽

Human Erythropoietin

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Protective effect of recombinant human erythropoietin in type II Gaucher disease patient cells by scavenging endoplasmic reticulum stress

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2011.04.019 ◽

2011 ◽

Vol 65 (5) ◽

pp. 364-368 ◽

Cited By ~ 3

Author(s):

Jeong-Rim Cha ◽

Sung-Jo Kim ◽

Tae-Hwe Heo

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Protective Effect ◽

Recombinant Human Erythropoietin ◽

Gaucher Disease ◽

Disease Patient ◽

Type Ii ◽

Human Erythropoietin

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Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats

Human & Experimental Toxicology ◽

10.1177/0960327117733553 ◽

2017 ◽

Vol 37 (8) ◽

pp. 848-858 ◽

Cited By ~ 1

Author(s):

K Rjiba-Touati ◽

I Amara ◽

M Bousabbeh ◽

I Ben Salem ◽

A Azzebi ◽

...

Keyword(s):

Oxidative Stress ◽

Recombinant Human Erythropoietin ◽

Wistar Rats ◽

Glutathione Depletion ◽

Control Group ◽

Protective Effects ◽

Drug Induced ◽

Human Erythropoietin ◽

Liver Tissues

Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.

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