N,N'-Diphenyl-1,4-phenylenediamine Antioxidant's Potential Role in Enhancing the Pancreatic Antioxidant, Immunomodulatory, and Anti-Apoptotic Therapeutic Capabilities of Adipose-Derived Stem Cells in Type I Diabetic Rats.

Abstract

Mesenchymal stem cells (MSCs) are considered to be a promising therapeutic protocol for diabetes mellitus (DM) management. The latter is attributed to their differentiation potentiality to pancreatic β-cells, angiogenesis, and immune-modulatory capabilities by releasing various paracrine factors. Interestingly, antioxidant co-administration increased the MSCs' hypoglycemic and regenerative activities. Thus, this study aims to evaluate the therapeutic implication of type 1 DM after the co-administration of adipose tissue-derived-MSCs (AD-MSCs) and N,N'-d iphenyl-1,4-phenylenediamine (DPPD), compared to the single injection of either of them alone. In our four week long experiment, six rat groups were used as control, DPPD (250 mg/kg, i.p.), STZ-diabetic (D), D+DPPD, D+AD-MSCs (1 × 106 cell/rat, i.p.), and D+AD-MSCs+DPPD groups. Within this context, a single injection of AD-MSCs or DPPD into diabetic rats showed significant pancreatic anti-inflammatory, immunomodulation, antioxidant, and anti-apoptotic capacities, superior to AD-MSCs injection. However, AD-MSCs and DPPD co-administration into diabetic rats manifested the highest hypoglycemic and pancreatic regenerative activities in managing diabetes compared to the single shot of AD-MSCs or DPPD. These results highlight the synergetic role of DPPD as an antioxidant in enhancing AD-MSCs' therapeutic applications.