Antioxidants, Vol. 12, Pages 58: 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

Conceptualization, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; methodology, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; software, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; validation, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; formal analysis, S.G.E.-S., H.M.R., M.K.D. and K.H.R.; investigation, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; resources, S.S., S.G.E.-S., H.M.R., M.K.D., K.H.R., E.I.E.-H., M.G., H.M.A.E.-L., H.E.-S. and M.M.K.; data curation, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; writing—original draft preparation, S.S., S.G.E.-S., H.M.R., M.K.D., K.H.R., E.I.E.-H., M.G., H.M.A.E.-L., H.E.-S. and M.M.K.; writing—review and editing, S.S., S.G.E.-S., H.E.-S., H.M.R., M.K.D., E.I.E.-H., M.G., H.M.A.E.-L., H.E.-S. and M.M.K.; visualization, S.G.E.-S., H.M.R. and E.I.E.-H.; supervision, S.G.E.-S., H.M.R., M.K.D., K.H.R. and E.I.E.-H.; project administration, S.S., S.G.E.-S., H.M.R., M.K.D., K.H.R., H.E.-S. and E.I.E.-H.; funding acquisition, S.S., M.G., H.M.A.E.-L., H.E.-S. and M.M.K. All authors have read and agreed to the published version of the manuscript.

Figure 1. Antioxidants N,N′-diphenyl-1,4-phenylenediamine.

Figure 1. Antioxidants N,N′-diphenyl-1,4-phenylenediamine.

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Figure 2. AD-MSCs positive surface markers (CD 73: 96.0%, CD 90: 96.7%, CD 105: 97.5%); AD-MSCs negative surface markers (CD 11b: 4.0%, CD 34: 4.6%, CD 45: 1.8%).

Figure 2. AD-MSCs positive surface markers (CD 73: 96.0%, CD 90: 96.7%, CD 105: 97.5%); AD-MSCs negative surface markers (CD 11b: 4.0%, CD 34: 4.6%, CD 45: 1.8%).

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Figure 3. (A) Serum glucose levels (mg/100 mL). Values expressed as ±SEM (n = 6). a, b are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group. (B) Serum insulin, C-peptide, and HbA1c levels. Values expressed as ±SEM (n = 6). a, b are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

Figure 3. (A) Serum glucose levels (mg/100 mL). Values expressed as ±SEM (n = 6). a, b are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group. (B) Serum insulin, C-peptide, and HbA1c levels. Values expressed as ±SEM (n = 6). a, b are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

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Figure 4. (A). Pancreatic oxidative stress (MDA and XO) levels and antioxidant markers (SOD and GST) levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group. (B). Pancreatic oxidative stress (H2O2 and AGEs) levels and antioxidant markers (CAT and TAC) levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group. (C). Pancreatic heme-oxygenase 1 oxidative stress levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

Figure 4. (A). Pancreatic oxidative stress (MDA and XO) levels and antioxidant markers (SOD and GST) levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group. (B). Pancreatic oxidative stress (H2O2 and AGEs) levels and antioxidant markers (CAT and TAC) levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group. (C). Pancreatic heme-oxygenase 1 oxidative stress levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

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Figure 5. Serum CRP & pancreatic TGF-β, CD95, and IL-6 levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

Figure 5. Serum CRP & pancreatic TGF-β, CD95, and IL-6 levels. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

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Figure 6. Pancreatic T-Helper (CD 4) and T-Cytotoxic (CD 8) %. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

Figure 6. Pancreatic T-Helper (CD 4) and T-Cytotoxic (CD 8) %. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

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Figure 7. Pancreatic P53, caspase 3, & Bcl-2%. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

Figure 7. Pancreatic P53, caspase 3, & Bcl-2%. Values expressed as ±SEM (n = 6). a, b & c are Significant differences (p ≤ 0.05) compared to control, diabetic untreated and DPPD-diabetic treated groups, respectively. % is the percent of change compared to the diabetic group.

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Table 1. Pancreatic cell cycle (G0/G1)%.

Table 1. Pancreatic cell cycle (G0/G1)%.

ControlDPPDDiabetic (D)D+DPPDD+AD-MSCsD+AD-
MSCs+DPPDG0/G1 phase (%)Mean ± SEM91.70 ± 3.1692.30 ± 3.3757.50 ± 1.22 a75.50 ± 2.43 ab85.00 ± 2.63 ab93.00 ± 3.25 bcS Phase (%)Mean ± SEM2.50 ± 0.012.70 ± 0.0211.00 ± 0.03 a6.50 ± 0.02 ab1.00 ± 0.01 ab2.50± 0.03 bcG2/M phase (%)Mean ± SEM2.80 ± 0.022.00 ± 0.026.50 ± 0.01 a1.70 ± 0.03 ab3.00 ± 0.01 ab2.70 ± 0.02 bc

Table 2. Pancreatic annexin V%.

Table 2. Pancreatic annexin V%.

ControlDPPDDiabetic (D)D+DPPDD+AD-MSCsD+AD-
MSCs+DPPDViable cells (%)Mean ± SEM93.70 ± 3.1692.50 ± 3.3733.20 ± 1.22 a63.50 ± 2.43 ab72.90 ± 2.63 ab93.00 ± 2.25 bcEarly apoptosis (%)Mean ± SEM0.50 ± 0.211.40 ± 0.453.50 ± 0.63 a15.00 ± 0.26 ab13.90 ± 0.98 ab0.60 ± 0.33 bcLate apoptosis (%)Mean ± SEM4.60 ± 1.424.80 ± 1.2229.00 ± 2.71 a21.80 ± 2.93 ab12.50 ± 2.26 ab6.50 ± 1.37 bcNecrosis (%)Mean ± SEM1.50 ± 0.121.40 ± 0.1635.70 ± 2.21 a0.20 ± 0.02 ab0.10 ± 0.01 ab0.30 ± 0.01 bc
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