Carbamylated Erythropoietin Alleviates Kidney Damage in Diabetic Rats by Suppressing Oxidative Stress

Curr Med Sci. 2021 Jun;41(3):513-521. doi: 10.1007/s11596-021-2370-x. Epub 2021 Jun 15.

Abstract

The oxidative stress response plays an important role in the occurrence and development of diabetic kidney disease (DKD). It has become a new treatment target for DKD. In the current study, the effects of carbamylated erythropoietin (CEPO) on renal oxidative stress and damage in diabetic rats were examined. Thirty Sprague Dawley rats were intraperitoneally administered with 60 mg/kg streptozotocin to establish the diabetes model. The diabetic rats were randomly allocated into 4 groups (n=6 each): diabetes model group (DM group), DM + CEPO treatment group (DC group), DM + CEPO + EPO receptor (EPOR) blocking peptide treatment group (DCEB group), and DM + CEPO + CD131 blocking peptide treatment group (DCCB group). Meanwhile, a normal control group (NC group, n=6) was set up. Kidney tissues and blood samples were obtained for evaluation of oxidative stress and renal function. The results showed that diabetic rats exhibited increased oxidative stress in the kidney and early pathological changes associated with DKD. Treatment with CEPO reduced oxidative stress and attenuated renal dysfunction. However, diabetic rats treated with the combination of CEPO and EPOR blocking peptide or CD131 blocking peptide showed increased oxidative stress and reduced renal function when compared with CEPO treatment alone group. These results suggested that CEPO can protect against kidney damage in DKD by inhibiting oxidative stress injury via EPOR-CD131 heterodimers.

Keywords: carbamylated erythropoietin; diabetic kidney disease; erythropoietin receptor; oxidative stress.

MeSH terms

  • Animals
  • Cytokine Receptor Common beta Subunit / genetics
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / pathology
  • Erythropoietin / analogs & derivatives*
  • Erythropoietin / genetics
  • Erythropoietin / pharmacology
  • Humans
  • Kidney / drug effects
  • Kidney / injuries
  • Kidney / pathology
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / toxicity

Substances

  • Cytokine Receptor Common beta Subunit
  • carbamylated erythropoietin
  • erythropoietin, rat
  • Erythropoietin
  • Streptozocin