Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Model
2.2. Chemicals
2.3. Echocardiographic Studies
2.4. Analysis of Serum Parameters
2.5. Morphometry
2.6. Histology
2.7. Western Blot
2.8. Cytochrome C Oxidase Enzyme Activity Microplate Assay
2.9. ATP Synthase Enzyme Activity Microplate Assay
2.10. Statistical Analyses
3. Results
3.1. BGP-15 Prevented Ageing and Type 2 Diabetes Mellitus-Associated Cardiac Dysfunction In Vivo
3.2. Severely Diabetic Rats Demonstrated Decreased Body Weight
3.3. Ageing and T2DM Elevates Serum Parameters
3.4. BGP-15 Has Mild Influence on Glucose Homeostasis
3.5. BPG-15 Decrease Myocardial Hypertrophy in Ageing Zucker Diabetic Fatty Rats
3.6. BGP-15 Improves Mitochondrial Function in Ageing Zucker Diabetic Fatty Rat Hearts
3.7. BGP-15 Treatment Induces MTCO and ATP Synthase Activity in Ageing Zucker Diabetic Fatty Rats
3.8. Ageing and T2DM Exerts an Antioxidant Response on ZDF Rat Hearts by HO-1 Dependent Activation
4. Discussion
4.1. General Characteristics of the ZDF Rats: Glucose and Lipid Homeostasis
4.2. Assessment of Cardiac Dysfunction and Remodelling
4.3. ROS Capacity
4.4. Upregulation of Cardiac ATP Synthase and Cytochrome C Oxidase
4.5. Translational Aspects and Future Directions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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LEAN | ZDF | ZDF+BGP-15 | ||
---|---|---|---|---|
N | 8 | 7 | 9 | |
Parameter | Unit | Mean ± SD | Mean ± SD | Mean ± SD |
BW | g | 453.6 ± 14.76 | # 279.3 ± 53.76 | # 279.9 ± 40.84 |
HW | g | 1.221 ± 0.15 | 1.09 ± 0.12 | # 1.02 ± 0.18 |
HW/TL | g/cm | 0.25 ± 0.05 | 0.24 ± 0.03 | 0.23 ± 0.04 |
BW/TL | g/cm | 91.14 ± 6.79 | # 60.13 ± 11.2 | # 58.86 ± 9.59 |
HW/BW | g/kg | 2.69 ± 0.36 | # 4 ± 0.7 | # 3.76 ± 0.95 |
lung w/d | 0.19 ± 0.02 | 0.19 ± 0.01 | 0.18 ± 0.01 | |
kidney w/d | 0.26 ± 0.03 | 0.23 ± 0.07 | 0.25 ± 0.03 |
LEAN | ZDF | ZDF+BGP-15 | ||
---|---|---|---|---|
N | 8 | 6 | 8 | |
Parameter | Unit | Mean ± SD | Mean ± SD | Mean ± SD |
Total Cholesterol | mmol/L | 2.19 ± 0.36 | # 8.09 ± 4.21 | # 5.62 ± 2.59 |
LDLc | mmol/L | 0.23 ± 0.08 | # 1.08 ± 0.68 | * 0.51 ± 0.33 |
HDLc | mmol/L | 0.49 ± 0.15 | 1.16 ± 0.68 | 0.69 ± 0.58 |
Creatinine | µmol/L | 26.7 ± 12.85 | # 141 ± 221.1 | # 66.88 ± 53.83 |
CK | U/L | 380.8 ± 304.6 | 548.8 ± 312.4 | * 182.1 ± 124.9 |
LDH | U/L | 1143 ± 1559 | 1871 ± 1256 | 1114 ± 856.8 |
Troponin T | ng/L | 3263 ± 2356 | 4162 ± 3293 | 3349 ± 2276 |
Control | ZDF | ZDF+BGP-15 | ||
---|---|---|---|---|
N | 8 | 6 | 8 | |
Parameter | Unit | Mean ± SD | Mean ± SD | Mean ± SD |
Glucose | mmol/litre | 7.05 ± 0.59 | # 18.42 ± 7.93 | * 10.74 ± 3.34 |
Insulin | mU/litre | 5.81 ± 1.48 | # 2.05 ± 1.02 | * 5.81 ± 1.48 |
HOMA-IR | 1.79 ± 0.40 | 1.87 ± 1.50 | # 3.19 ± 0.88 | |
HOMA-B | 13.3 ± 5.15 | # −0.89 ± 1.54 | * 11.92 ± 10.57 |
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Kozma, M.; Bombicz, M.; Varga, B.; Priksz, D.; Gesztelyi, R.; Tarjanyi, V.; Kiss, R.; Szekeres, R.; Takacs, B.; Menes, A.; Balla, J.; Balla, G.; Szilvassy, J.; Szilvassy, Z.; Juhasz, B. Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity. Pharmaceutics 2022, 14, 226. https://doi.org/10.3390/pharmaceutics14020226
Kozma M, Bombicz M, Varga B, Priksz D, Gesztelyi R, Tarjanyi V, Kiss R, Szekeres R, Takacs B, Menes A, Balla J, Balla G, Szilvassy J, Szilvassy Z, Juhasz B. Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity. Pharmaceutics. 2022; 14(2):226. https://doi.org/10.3390/pharmaceutics14020226
Chicago/Turabian StyleKozma, Mate, Mariann Bombicz, Balazs Varga, Daniel Priksz, Rudolf Gesztelyi, Vera Tarjanyi, Rita Kiss, Reka Szekeres, Barbara Takacs, Akos Menes, Jozsef Balla, Gyorgy Balla, Judit Szilvassy, Zoltan Szilvassy, and Bela Juhasz. 2022. "Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity" Pharmaceutics 14, no. 2: 226. https://doi.org/10.3390/pharmaceutics14020226