Therapeutic effect of N, N-Diphenyl-1,4-phenylenediamine and adipose-derived stem cells coadministration on diabetic cardiomyopathy in type 1 diabetes mellitus-rat model

J Exp Zool A Ecol Integr Physiol. 2024 Jul;341(6):647-657. doi: 10.1002/jez.2810. Epub 2024 Apr 9.

Abstract

Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.

Keywords: DPPD; antioxidant; diabetic cardiomyopathy; mesenchymal stem cells; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue
  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / therapy
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / therapy
  • Diabetic Cardiomyopathies* / therapy
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells
  • Oxidative Stress / drug effects
  • Phenylenediamines / administration & dosage
  • Phenylenediamines / pharmacology
  • Rats
  • Rats, Wistar*

Substances

  • Phenylenediamines