Role of recombinant human erythropoietin against mitomycin C-induced cardiac, hepatic and renal dysfunction in Wistar rats

Hum Exp Toxicol. 2015 May;34(5):468-78. doi: 10.1177/0960327114550885. Epub 2014 Oct 10.

Abstract

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.

Keywords: Mitomycin C; chemotherapy; heart protection; kidney protection; liver protection; recombinant human erythropoietin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Cardiotoxicity
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Drug Administration Schedule
  • Erythropoietin / administration & dosage
  • Erythropoietin / therapeutic use*
  • Heart Failure / blood
  • Heart Failure / chemically induced
  • Heart Failure / pathology
  • Heart Failure / prevention & control*
  • Kidney Function Tests
  • Liver Function Tests
  • Male
  • Mitomycin / adverse effects*
  • Organ Size / drug effects
  • Rats, Wistar
  • Recombinant Proteins
  • Renal Insufficiency / blood
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / pathology
  • Renal Insufficiency / prevention & control*

Substances

  • Antibiotics, Antineoplastic
  • EPO protein, human
  • Recombinant Proteins
  • Erythropoietin
  • Mitomycin