Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice
Diabetes is associated with aldosterone excess and the overactivation of its mineralocorticoid receptor (MR) which leads to the development of many cardiovascular dysfunctions. Therefore, MR antagonists have been found to exert favorable effects on the cardiovascular system. Finerenone is a new nons...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223017080 |
| _version_ | 1797404571085045760 |
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| author | Bielicka Natalia Misztal Tomasz Chabielska Ewa Gromotowicz-Popławska Anna |
| author_facet | Bielicka Natalia Misztal Tomasz Chabielska Ewa Gromotowicz-Popławska Anna |
| author_sort | Bielicka Natalia |
| collection | DOAJ |
| description | Diabetes is associated with aldosterone excess and the overactivation of its mineralocorticoid receptor (MR) which leads to the development of many cardiovascular dysfunctions. Therefore, MR antagonists have been found to exert favorable effects on the cardiovascular system. Finerenone is a new nonsteroidal MR antagonist approved for the treatment of chronic kidney disease associated with type 2 diabetes. Clinical studies have demonstrated that finerenone improves cardiovascular outcomes. However, its influence on hemostasis in the cardioprotective effect is unknown. Therefore, the main aim of our study was to evaluate the effects of finerenone (10 mg/kg, p.o.) on selected hemostasis parameters in streptozotocin (180 mg/kg, i.p.)-induced diabetes. Since regulation of the MR activity is sex-dependent, the study was conducted in both female and male mice. The most beneficial effects of finerenone were observed in diabetic female mice which included a decrease in thrombus formation, attenuation of platelet activity, inhibition of the coagulation system, and activation of fibrinolysis. In contrast, in male diabetic mice only an attenuation of the coagulation system was observed. Furthermore, finerenone also exerted unfavorable effects, but only in normoglycemic mice, manifested as a slight increase in platelet activity in males and an enhancement of the coagulation system activity in females. Our study is the first to show the sex-dependent and glycemia-dependent effects of finerenone on hemostasis in diabetes. The occurrence of beneficial effects only in female diabetic mice requires in-depth study. |
| first_indexed | 2024-03-09T02:56:56Z |
| format | Article |
| id | doaj.art-5705d1ef4f1b4e0882f7b05945249cc9 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-09T02:56:56Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-5705d1ef4f1b4e0882f7b05945249cc92023-12-05T04:14:46ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115910Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic miceBielicka Natalia0Misztal Tomasz1Chabielska Ewa2Gromotowicz-Popławska Anna3Department of Biopharmacy and Radiopharmacy, Medical University of Bialystok, ul. Mickiewicza 2C, 15-222 Bialystok, Poland; Corresponding author.Department of Physical Chemistry, Medical University of Bialystok, ul. Mickiewicza 2A, 15-089 Bialystok, PolandDepartment of Biopharmacy and Radiopharmacy, Medical University of Bialystok, ul. Mickiewicza 2C, 15-222 Bialystok, PolandDepartment of Biopharmacy and Radiopharmacy, Medical University of Bialystok, ul. Mickiewicza 2C, 15-222 Bialystok, PolandDiabetes is associated with aldosterone excess and the overactivation of its mineralocorticoid receptor (MR) which leads to the development of many cardiovascular dysfunctions. Therefore, MR antagonists have been found to exert favorable effects on the cardiovascular system. Finerenone is a new nonsteroidal MR antagonist approved for the treatment of chronic kidney disease associated with type 2 diabetes. Clinical studies have demonstrated that finerenone improves cardiovascular outcomes. However, its influence on hemostasis in the cardioprotective effect is unknown. Therefore, the main aim of our study was to evaluate the effects of finerenone (10 mg/kg, p.o.) on selected hemostasis parameters in streptozotocin (180 mg/kg, i.p.)-induced diabetes. Since regulation of the MR activity is sex-dependent, the study was conducted in both female and male mice. The most beneficial effects of finerenone were observed in diabetic female mice which included a decrease in thrombus formation, attenuation of platelet activity, inhibition of the coagulation system, and activation of fibrinolysis. In contrast, in male diabetic mice only an attenuation of the coagulation system was observed. Furthermore, finerenone also exerted unfavorable effects, but only in normoglycemic mice, manifested as a slight increase in platelet activity in males and an enhancement of the coagulation system activity in females. Our study is the first to show the sex-dependent and glycemia-dependent effects of finerenone on hemostasis in diabetes. The occurrence of beneficial effects only in female diabetic mice requires in-depth study.http://www.sciencedirect.com/science/article/pii/S0753332223017080FinerenoneSexThrombosisHemostasisPlateletsDiabetes |
| spellingShingle | Bielicka Natalia Misztal Tomasz Chabielska Ewa Gromotowicz-Popławska Anna Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice Biomedicine & Pharmacotherapy Finerenone Sex Thrombosis Hemostasis Platelets Diabetes |
| title | Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice |
| title_full | Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice |
| title_fullStr | Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice |
| title_full_unstemmed | Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice |
| title_short | Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice |
| title_sort | sex dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin induced diabetic mice |
| topic | Finerenone Sex Thrombosis Hemostasis Platelets Diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223017080 |
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