Beta-Blockers of Different Generations: Features of Influence on the Disturbances of Myocardial Energy Metabolism in Doxorubicin-Induced Chronic Heart Failure in Rats
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Experimental Model
2.3. Drugs and Pharmacological Agents
2.4. Anesthesia
2.5. Preparation of Biological Material Experimental Model
2.6. Biochemical Assays and Techniques
2.6.1. Determination of Adenyl Nucleotides by Thin-Layer Chromatography
- -
- Isopropanol;
- -
- Dioxane;
- -
- Ammonia;
- -
- Plates for thin-layer chromatography on an aluminum substrate coated with a microfractionated silica gel sorbent.
2.6.2. Quantitative Determination of Pyruvate Content Using the Zoch–Lamprecht Method
- -
- 0.5 M tris-HCl-aminomethane buffer, pH 7.6;
- -
- 0.06 M NADH solution;
- -
- lactate dehydrogenase (activity 700 units/mg).
- V—the final sample volume in the cuvette;
- K—the dilution factor of the sample relative to the tissue.
2.6.3. Quantitative Determination of Malate Using the Hohorst Method
- -
- 0.4 M hydrazine–glycine buffer, pH 9.5;
- -
- 0.05 M NAD+ solution;
- -
- malate dehydrogenase (activity 700 units/mg).
- V—the final sample volume in the cuvette;
- K—the dilution factor of the sample relative to the tissue.
2.6.4. Determination of Succinate Dehydrogenase (SDH) Activity
- -
- 0.1 M succinic acid;
- -
- 25 mM potassium hexacyanoferroate (III);
- -
- 150 mM sodium azide;
- -
- 25 mM EDTA (pH 7.8);
- -
- 0.1 M phosphate buffer (pH 7.8);
- -
- 20% trichloroacetic acid (TCA).
- a—protein content in the sample, mg;
- M—molecular weight of potassium hexacyanoferroate (III);
- t—incubation time, min.
2.6.5. Determination of Lactate Content Using the Hohorst Method
- -
- 0.4 M hydrazine–glycine buffer pH 9.5;
- -
- 0.05 M NAD solution;
- -
- lactate dehydrogenase (activity 700 units/mg).
- V—the final sample volume in the cuvette;
- K—the dilution factor of the sample relative to the tissue.
2.6.6. Determination of NAD-Dependent Malate Dehydrogenase Activity
- V—final sample volume (3 mL);
- 6.22 micromolar extinction coefficient of NADH at 340 nm;
- is the protein concentration in the sample.
2.6.7. Opening of the Mitochondrial Pore (MP)
2.7. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Group of Animals | ATP, µmol/g Tissue | ADP, µmol/g Tissue | AMP, µmol/g Tissue |
---|---|---|---|
Intact (n = 10) | 3.8 ± 0.21 | 0.57 ± 0.02 | 0.154 ± 0.007 |
CHF (control) (n = 6) | 1.9 ± 0.12 1 | 0.33 ± 0.017 1 | 0.27 ± 0.014 1 |
CHF + Hypertril, 3.5 mg/kg (n = 19) | 2.7 ± 0.12 *1 | 0.41 ± 0.010 *1 | 0.169 ± 0.011 *1 |
CHF + Carvedilol 50 mg/kg (n = 10) | 2.2 ± 0.09 1 | 0.36 ± 0.017 1 | 0.25 ± 0.017 1 |
CHF + Nebivalol, 10 mg/kg (n = 16) | 2.3 ± 0.07 *1 | 0.36 ± 0.021 1 | 0.23 ± 0.011 *1 |
CHF + Bisoprolol, 10 mg/kg (n = 16) | 1.85 ± 0.14 1 | 0.35 ± 0.033 1 | 0.26 ± 0.034 1 |
CHF + Metoprolol, 15 mg/kg | 1.9 ± 0.11 1 | 0.34 ± 0.054 1 | 0.25 ± 0.017 1 |
Group of Animals | Lactate, µmol/g Tissue | Malate, µmol/g Tissue | Pyruvate, µmol/g Tissue |
---|---|---|---|
Intact (n = 10) | 5.2 ± 0.31 | 0.36 ± 0.02 | 0.15 ± 0.01 |
CHF (control) (n = 6) | 12.1 ± 0.87 1 | 0.11 ± 0.01 1 | 0.071 ± 0.001 1 |
CHF + Hypertril, 3.5 mg/kg (n = 19) | 7.4 ± 0.44 *1 | 0.21 ± 0.01 *1 | 0.088 ± 0.001 *1 |
CHF + Carvedilol 50 mg/kg (n = 10) | 10.2 ± 0.92 1 | 0.12 ± 0.02 | 0.072 ± 0.001 1 |
CHF + Nebivalol, 10 mg/kg (n = 16) | 8.10 ± 0.54 *1 | 0.14 ± 0.01 *1 | 0.080 ± 0.001 *1 |
CHF + Bisoprolol, 10 mg/kg(n = 16) | 11.5 ± 0.42 1 | 0.12 ± 0.01 1 | 0.072 ± 0.003 1 |
CHF + Metoprolol, 15 mg/kg | 11.1 ± 1.2 | 0.12 ± 0.01 1 | 0.065 ± 0.002 |
Group of Animals | Lactate, µmol/g Tissue | NAD-MDH, μmol/mg Protein/min | SDH, nmol/mg Protein/min | MPTP Opening, ∆E 540 nm | MMP, (Ψ) | ATP, µmol/g Tissue |
---|---|---|---|---|---|---|
Intact (n = 10) | 1.5 ± 0.08 | 1.71 ± 0.08 | 5.5 ± 0.28 | 0.052 ± 0.002 | 52.1 ± 3.2 | 2.7 ± 0.12 |
CHF (control) (n = 6) | 2.7 ± 0.14 1 | 0.65 ± 0.04 1 | 1.8 ± 0.10 1 | 0.63 ± 0.022 1 | 18.2 ± 1.0 1 | 1.2 ± 0.03 1 |
CHF + Hypertril, 3.5 mg/kg (n = 19) | 1.7 ± 0.15 * | 1.14 ± 0.08 *1 | 3.1 ± 0.17 *1 | 0.31 ± 0.005 *1 | 33.2 ± 2.4 *1 | 1.60 ± 0.15 *1 |
CHF + Carvedilol 50 mg/kg (n = 10) | 2.5 ± 0.19 1 | 0.67 ± 0.01 1 | 2.2 ± 0.14 *1 | 0.44 ± 0.011 *1 | 25.4 ± 1.2 *1 | 1.3 ± 0.11 1 |
CHF + Nebivalol, 10 mg/kg (n = 16) | 2.2 ± 0.10 *1 | 0.79 ± 0.04 *1 | 2.6 ± 0.11 *1 | 0.47 ± 0.007 *1 | 25.7 ± 1.8 *1 | 1.42 ± 0.07 *1 |
CHF + Bisoprolol, 10 mg/kg (n = 16) | 2.3 ± 0.18 *1 | 0.67 ± 0.02 1 | 2.0 ± 0.22 1 | 0.63 ± 0.015 1 | 18.8 ± 2.7 1 | 1.2 ± 0.25 1 |
CHF + Metoprolol, 15 mg/kg | 2.5 ± 0.21 1 | 0.68 ± 0.03 1 | 2.1 ± 0.19 1 | 0.65 ± 0.011 1 | 19.3 ± 3.0 1 | 1.2 ± 0.10 1 |
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Belenichev, I.; Goncharov, O.; Bukhtiyarova, N.; Kuchkovskyi, O.; Ryzhenko, V.; Makyeyeva, L.; Oksenych, V.; Kamyshnyi, O. Beta-Blockers of Different Generations: Features of Influence on the Disturbances of Myocardial Energy Metabolism in Doxorubicin-Induced Chronic Heart Failure in Rats. Biomedicines 2024, 12, 1957. https://doi.org/10.3390/biomedicines12091957
Belenichev I, Goncharov O, Bukhtiyarova N, Kuchkovskyi O, Ryzhenko V, Makyeyeva L, Oksenych V, Kamyshnyi O. Beta-Blockers of Different Generations: Features of Influence on the Disturbances of Myocardial Energy Metabolism in Doxorubicin-Induced Chronic Heart Failure in Rats. Biomedicines. 2024; 12(9):1957. https://doi.org/10.3390/biomedicines12091957
Chicago/Turabian StyleBelenichev, Igor, Olexiy Goncharov, Nina Bukhtiyarova, Oleh Kuchkovskyi, Victor Ryzhenko, Lyudmyla Makyeyeva, Valentyn Oksenych, and Oleksandr Kamyshnyi. 2024. "Beta-Blockers of Different Generations: Features of Influence on the Disturbances of Myocardial Energy Metabolism in Doxorubicin-Induced Chronic Heart Failure in Rats" Biomedicines 12, no. 9: 1957. https://doi.org/10.3390/biomedicines12091957