Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Results
2.1. Metabolic and Renal Biochemicals Profiles
2.2. Markers of Renal Tissue Damage
2.3. Renal Metabolic Regulatory Molecules
2.3.1. Renal Glucose Transporting Proteins
2.3.2. Renal Lipid Regulatory Molecules
2.3.3. Renal Tissue Concentrations of Adipokines
2.4. Renal Tissue Concentrations of Inflammatory and Oxidative Stress Markers
3. Discussion
4. Materials and Methods
4.1. Ethical Statement
4.2. Drugs
4.3. Induction of Diabetic Nephropathy and Treatment Protocols
4.4. Samples Collection and Processing
4.5. Quantitative RT-PCR
4.6. Immunohistochemistry (IHC)
4.7. Cell Apoptosis and Expression of Cleaved Caspase-3 Protein
4.8. Western Blotting
4.9. Enzyme-Linked Immunosorbent Assay (ELISA)
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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NC Group | PC Group | SGLT2i Group | Pcal Group | SG-P Group | ||
---|---|---|---|---|---|---|
Body Weight (g) * | 34.5 ± 3.4 | 22.2 ± 1.3 b | 28.7 ± 3.6 b,d | 24.8 ± 2.4 b,e | 32.4 ± 2.5 d,e,g | |
Serum | FBG (mg/dL) * | 81.3 ± 7.1 | 294.5 ± 14.6 b | 127.8 ± 13.7 b,d | 179.4 ± 10.9 b,d,f | 100.9 ± 11.5 a,d,f,h |
Insulin (μU/mL) ** | 27.3 ± 5.7 | 5.9 ± 1.3 b | 10.8 ± 2.2 b,d | 8.4 ± 1.8 b,c | 18.1 ± 3.2 b,d,f,g | |
Total Cholesterol (mmol/L) ** | 1.5 ± 0.14 | 2.91 ± 0.09 b | 2.1 ± 0.22 b,d | 2.4 ± 0.25 b,d | 1.71 ± 0.12 a,d,f,g | |
LDL (mmol/L) ** | 0.37 ± 0.06 | 1.82 ± 0.18 b | 0.92 ± 0.16 b,d | 1.32 ± 0.17 b,d,f | 0.67 ± 0.15 b,d,e,g | |
HDL (mmol/L) ** | 1.1 ± 0.13 | 0.47 ± 0.1 b | 0.78 ± 0.07 b,d | 0.65 ± 0.07 b,d,f | 0.96 ± 0.14 d,e,g | |
Triglycerides (mmol/L) * | 0.76 ± 0.12 | 1.73 ± 0.13 b | 1.1 ± 0.15 b,d | 1.35 ± 0.1 b,d,f | 0.91 ± 0.09 a,d,e,g | |
Total protein (g/dL) * | 6.9 ± 0.87 | 4.46 ± 0.58 b | 5.38 ± 0.53 b,c | 4.92 ± 0.62 b | 6.11 ± 0.7 d,g | |
Albumin (g/dL) * | 4.1 ± 0.7 | 2.3 ± 0.4 b | 2.92 ± 0.39 b,c | 2.7 ± 0.34 b | 3.53 ± 0.45 d,e,g | |
Creatinine (mg/dL) * | 0.44 ± 0.1 | 1.25 ± 0.16 b | 0.69 ± 0.11 b,d | 0.82 ± 0.1 b,d | 0.53 ± 0.1 d,e,g | |
Urea (mg/dL) ** | 35.6 ± 5.1 | 76.2 ± 9.4 b | 48.2 ± 5.7 b,d | 57.4 ± 5.6 b,d,e | 41.5 ± 5.4 d,g | |
Spot Urine | Creatinine (mg/dL) ** | 45.2 ± 7.3 | 22.1 ± 2.9 b | 39.8 ± 4 d | 36.7 ± 4.2 b | 41.1 ± 3.7 d |
Total protein (mg/dL) ** | 4.3 ± 0.8 | 22.8 ± 2.7 b | 14.7 ± 2.5 b,d | 19.1 ± 2.4 b,c,f | 7.3 ± 1.6 a,d,f,g | |
Protein/Cr ratio (mg/g) ** | 95.6 ± 21.3 | 1057.1 ± 240.3 b | 368.2 ± 50.9 b,d | 684.3 ± 65.6 b,d,f | 179.5 ± 43.5 b,d,f,g |
NC Group | PC Group | SGLT2i Group | Pcal Group | SG-P Group | |
---|---|---|---|---|---|
TNF-α (pg/mL) ** | 29.3 ± 4.7 | 95.2 ± 9.9 a | 56.6 ± 8.7 a,c | 51.7 ± 8.5 a,c | 34.4 ± 3.8 c,e,g |
IL1β (pg/mL) ** | 24.6 ± 5.8 | 233.3 ± 17.2 a | 150.9 ± 16.8 a,c | 178.2 ± 16.3 a,c,d | 52.2 ± 6.1 a,c,e,g |
IL6 (pg/mL) ** | 29.2 ± 4.8 | 126.8 ± 7.9 a | 87.9 ± 10.9 a,c | 73.8 ± 7.8 a,c,d | 41.7 ± 6.5 a,c,e,g |
IL10 (pg/mL) ** | 51.6 ± 9.3 | 13.2 ± 2.7 a | 27.6 ± 6.4 a,c | 25.3 ± 3.7 a,c | 43.3 ± 5.7 c,e,g |
GSH (mg/g) * | 38.3 ± 5.3 | 17.5 ± 5.9 a | 24.6 ± 4.8 a,b | 27.3 ± 3.7 a,c | 34.7 ± 5.2 c,e,f |
GPx1 (µg/mg) * | 4.1 ± 0.8 | 2.1 ± 0.4 a | 2.8 ± 0.5 a | 3.0 ± 0.6 a,b | 3.9 ± 0.6 c,e,f |
SOD1 (U/g) * | 45.2 ± 5.6 | 21.7 ± 4.5 a | 28.5 ± 4.1 a,b | 29.3 ± 4.1 a,c | 37.8 ± 3.4 a,c,e,g |
CAT (U/mg) ** | 253.2 ± 18.1 | 142.2 ± 24.4 a | 183.7 ± 22.7 a,c | 164.7 ± 12.1 a | 217.9 ± 9.9 a,c,e,g |
MDA (nmol/g) * | 34.6 ± 3.8 | 65.1 ± 6.2 a | 53.7 ± 6.1 a,c | 52.4 ± 7.3 a,c | 38.8 ± 6.1 c,e,g |
H2O2 (μM/g) ** | 1.2 ± 0.2 | 68.2 ± 7.6 a | 28.4 ± 6.9 a,c | 25.6 ± 7.2 a,c | 4.6 ± 1.2 a,c,e,g |
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Mujalli, A.; Farrash, W.F.; Obaid, A.A.; Khan, A.A.; Almaimani, R.A.; Idris, S.; Elzubier, M.E.; Khidir, E.B.A.; Aslam, A.; Minshawi, F.; et al. Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2023, 24, 17380. https://doi.org/10.3390/ijms242417380
Mujalli A, Farrash WF, Obaid AA, Khan AA, Almaimani RA, Idris S, Elzubier ME, Khidir EBA, Aslam A, Minshawi F, et al. Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2023; 24(24):17380. https://doi.org/10.3390/ijms242417380
Chicago/Turabian StyleMujalli, Abdulrahman, Wesam F. Farrash, Ahmad A. Obaid, Anmar A. Khan, Riyad A. Almaimani, Shakir Idris, Mohamed E. Elzubier, Elshiekh Babiker A. Khidir, Akhmed Aslam, Faisal Minshawi, and et al. 2023. "Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus" International Journal of Molecular Sciences 24, no. 24: 17380. https://doi.org/10.3390/ijms242417380