Abstract
Aging is known as a main risk factor in the development of cardiovascular diseases. Naringin (NRG) is a flavonoid compound derived from citrus fruits. It possesses a wide spectrum of pharmacological properties, including antioxidant anti-inflammatory, and cardioprotective. This investigation aimed to assess the cardioprotective effect of NRG against the ischemia/reperfusion (I/R) injury in aged rats. In this study, D-galactose (D-GAL) at the dose of 150 mg/kg/day for 8 weeks was used to induce aging in rats. Rats were orally gavaged with NRG (40 or 100 mg/kg/day), in co-treatment with D-GAL, for 8 weeks. The Langendorff isolated heart was used to evaluate the effect of NRG on I/R injury in aged rats. NRG treatment diminished myocardial hypertrophy and maximum contracture level in aged animals. During the pre-ischemic phase, reduced heart rate was normalized by NRG. The effects of D-GAL on the left ventricular end diastolic pressure (LVDP), the rate pressure product (RPP), and the minimum and maximum rate of left ventricular pressure (±dp/dt) improved by NRG treatment in the perfusion period. NRG also enhanced post-ischemic recovery of cardiac functional parameters (± dp/dt, and RPP) in isolated hearts. An increase in serum levels of the lactate dehydrogenase (LDH), the creatine kinase-MB (CK-MB), and the tumor necrosis factor-alpha (TNF-α) were reversed by NRG in aged rats. It also normalized the D-GAL-decreased the superoxide dismutase (SOD) activity in the heart tissue. NRG treatment alleviated cardiac injury in aged hearts under conditions of I/R. NRG may improve aging-induced cardiac dysfunction through anti-oxidative and anti-inflammatory mechanisms.
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Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Abbreviations
- ANOVA:
-
Analysis of variance
- BW:
-
Body weight
- CaCl2:
-
Calcium chloride
- CF:
-
Coronary flow
- CK-MB:
-
Creatine kinase-MB
- CVDs:
-
Cardiovascular diseases
- D-GAL:
-
D-Galactose
- dp/dt Max :
-
Maximum rate of left ventricular pressure
- dp/dt Min :
-
Minimum rate of left ventricular pressure
- ELISA:
-
Enzyme-linked immunosorbent assay
- GCL:
-
Glutamate cysteine ligase
- GPx:
-
Glutathione peroxidase
- HR:
-
Heart rate
- HO-1:
-
Heme oxygenase-1
- HW:
-
Heart weight
- I/R:
-
Ischemia/reperfusion
- KCl:
-
Potassium chloride
- KH2PO4:
-
Potassium dihydrogenephosphate
- LDH:
-
Lactate dehydrogenase
- LVDP:
-
Left ventricular developed pressure
- LVEDP:
-
Left ventricular end diastolic pressure
- LVSP:
-
Left ventricular systolic pressure
- MC:
-
Maximum contracture
- MgSO4:
-
Magnesium sulfate
- MI:
-
Myocardial infarction
- NaCl:
-
Sodium chloride
- NaHCO3:
-
Sodium bicarbonate
- NOAEL:
-
No-observed-adverse-effect level
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- NRG:
-
Naringin
- PBS:
-
Phosphate buffer saline
- ROS:
-
Reactive oxygen species
- RPP:
-
Rate pressure product
- SD:
-
Standard deviation
- SEM:
-
Standard error of measurement
- SOD:
-
Superoxide dismutase
- TNF-α:
-
Tumor necrosis factor-alpha
- U/L:
-
Units per liter of sample
- U/mg:
-
Unit per milligram
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Acknowledgements
The authors are grateful to the Kermanshah University of Medical Sciences, Health Technology Institute, Medical Biology Research Center, Kermanshah, Iran, for financial support.
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This work was supported by Kermanshah University of Medical Sciences, Kermanshah, Iran (IR.KUMS.REC.1397.902).
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D. Sh. contributed to data collection and interpretation, and wrote the manuscript, M. H. performed the experiments, and contributed reagents, S. R-A. Contributed reagents, materials, and analysis tools or data, M. P. conceived and designed the experiments, F. Y. contributed to data collection and analysis, and wrote the manuscript, F. R-A. Designed the study, contributed to data collection and interpretation, and wrote the manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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This study was approved by the Animal Ethics Committee of Kermanshah University of Medical sciences (Ethics Committee Permission No. IR.KUMS.REC.1397.902).
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Shackebaei, D., Hesari, M., Ramezani-Aliakbari, S. et al. Cardioprotective effect of naringin against the ischemia/reperfusion injury of aged rats. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1209–1218 (2024). https://doi.org/10.1007/s00210-023-02692-2
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DOI: https://doi.org/10.1007/s00210-023-02692-2