Balaji, S and Patnaik, YR and Surin, WR (2024) Off-target effect of high-dose sildenafil on adenosine 5�-diphosphate and collagen-induced platelet activation through mitogen-activated protein kinase pathway in treated BALB/C mice and in vitro experiments: A preliminary study. In: Wolters Kluwer Medknow Publications, 56 (2). pp. 136-140.
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Abstract
Sildenafil, a common over-the-counter pill often self-administered at high doses for erectile dysfunction, has been reported to rarely cause prothrombotic events and sudden cardiac death in a few case reports. Therefore, we investigated the in vitro and in vivo effect of sildenafil treatment and dosage on platelet activation and mitogen-activated protein kinase (MAPK) phosphorylation. BALB/C mice were segregated into four groups, each having four mice each (control, low 3.25 mg/kg, medium 6.5 mg/kg, and high 13 mg/kg sildenafil), and after the treatment, blood was drawn from each mouse and washed platelets prepared. Washed platelets were incubated with CD41 PE-Cy7 and Phospho-p38 MAPK PE antibodies and analyzed using a flow cytometer for platelet activation and adenosine 5'- diphosphate (ADP)/collagen-induced MAPK phosphorylation. Washed platelets obtained from the venous blood of 18 human volunteers, were incubated with PAC-1 FITC and Phospho-p38 MAPK PE antibodies, and platelet activation (ADP and collagen), followed by flow cytometry analysis. There was a significant increase in both platelet activation as well as MAPK phosphorylation in the presence of collagen in the high-dose (13 mg/kg) sildenafil group (P = 0.000774). Further, increased platelet activation was observed in samples that were treated with high-dose sildenafil as compared to the untreated samples (P < 0.00001). These studies show the risk of prothrombotic episodes in patients on high-dose sildenafil (100 mg), in those with even mild endothelial dysfunction due to ADP, and collagen-induced platelet activation through MAPK phosphorylation, which was not seen in the low-and intermediate-dose cohorts. © 2024 Copyright:
| Item Type: | Journal Article |
|---|---|
| Publication: | Wolters Kluwer Medknow Publications |
| Publisher: | Wolters Kluwer Medknow Publications |
| Additional Information: | The copyright for this article belongs to authors. |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 09 Jun 2024 08:42 |
| Last Modified: | 09 Jun 2024 08:42 |
| URI: | http://eprints.iisc.ac.in/id/eprint/85038 |
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