Abstract
Coronary artery diseases are principal sources of mortality and disability in global human population. Progressively, rivaroxaban is being evaluated for the prevention of atherosclerotic thrombi, particularly with anti-platelet agents. Hence, the current report aimed to investigate the cardioprotective effect of rivaroxaban on isoproterenol (ISO)-induced cardiac injury model in rats and the possible synergistic effect when combined with aspirin. Male Wistar rats were randomly assigned into five different groups. Cardiac injury was induced by subcutaneous injection of ISO (85 mg/kg) for 2 consecutive days. Rat tail bleeding time was performed prior to sacrifice. Cardiac enzymes, platelet activity, inflammatory, and oxidative stress biomarkers levels were measured using enzyme-linked immunoassay (ELISA). Pre-administration of rivaroxaban alone and on combination with aspirin prevented ISO-induced increase in cardiac thiobarbituric acid reactive substances (TBARS), interleukin 6 (IL-6), and thromboxane B2 (TXB2) levels. Moreover, a significant prolongation of bleeding time was demonstrated among aspirin, rivaroxaban, and aspirin plus rivaroxaban treated groups. On the other hand, the combination treatment of aspirin plus rivaroxaban showed no marked difference in these biomarkers and bleeding time relative to either drug administered separately. However, a prominent decrease of cardiac 6-keto prostaglandin F1α (6-Keto-PGF1α) level was displayed in the combination treatment when compared with ISO and rivaroxaban-treated groups, whereas no significant improvement was seen in cardiac glycoprotein V (GPV) levels except in aspirin-treated group. The study results demonstrated that rivaroxaban decreases cardiac oxidative stress, inflammation, and platelets reactivity. However, the addition of rivaroxaban to aspirin did not seem to show synergistic antioxidant, anti-inflammatory, or antiplatelet effect.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- CVD:
-
Cardiovascular disease
- LDL:
-
Low density lipoproteins
- MMPs:
-
Matrix metalloproteinases
- GP:
-
Glycoprotein
- TXA2:
-
Thromboxane A2
- ADP:
-
Adenosine diphosphate
- ISO:
-
Isoproterenol
- MI:
-
Myocardial infarction
- VKAs:
-
Vitamin K antagonists
- TF:
-
Tissue factor
- JUST:
-
Jordan University of Science and Technology
- ACUC:
-
Animal Care and Use Committee
- PBS:
-
Phosphate-buffered saline
- AST:
-
Aspartate aminotransferase
- ALT:
-
Alanine aminotransferase
- CK:
-
Creatine kinase
- LDH:
-
Lactate dehydrogenase
- TNF-α:
-
Tumor necrosis alpha
- IL-6:
-
Interleukin-6
- NO:
-
Nitric oxide
- SOD:
-
Superoxide dismutase
- TBARS:
-
Thiobarbituric acid-reactive substances
- TXB2:
-
Thromboxane B2
- 6-Keto-PGF1α:
-
6-Keto-prostaglandin F1 alpha
- GPV:
-
Glycoprotein V
- Hwt/Bwt:
-
Heart weight to body weight
- PAR:
-
Protease-activated receptors
- COX:
-
Cyclooxygenase
- ELISA:
-
Enzyme-linked immunoassay
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This work was supported by the Deanship of Research at Jordan University of Science and Technology [Grant No. 369–2021 to AR].
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AR, NA, and MA designed the study. AR and NA conducted the experimental work. AR, NA, and MA drafted the manuscript; AR and NA conducted the field research; AR contributed new reagents or analytic tools; AR, NA, and MA performed data analysis and interpreted the results; AR and NA contributed to the discussion. All authors read and approved the final manuscript.
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Abedalqader, N.N., Rababa’h, A.M. & Ababneh, M. The protective effect of rivaroxaban with or without aspirin on inflammation, oxidative stress, and platelet reactivity in isoproterenol-induced cardiac injury in rats. Naunyn-Schmiedeberg's Arch Pharmacol 396, 337–351 (2023). https://doi.org/10.1007/s00210-022-02319-y
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DOI: https://doi.org/10.1007/s00210-022-02319-y