Repurposing of Sildenafil as Hepatoprotective in Sinusoidal Obstruction Syndrome: Amendment of Endothelial Cell Damage and Inhibition of Platelet Aggregation
Mansour, M., Gad, A., Zaky, H., Abdel Baky, N. (2021). Repurposing of Sildenafil as Hepatoprotective in Sinusoidal Obstruction Syndrome: Amendment of Endothelial Cell Damage and Inhibition of Platelet Aggregation. EKB Journal Management System, 1(3), 21-31. doi: 10.21608/aijpms.2021.206681
Mona Mansour; Amany Gad; Heba Zaky; Nayira Abdel Baky. "Repurposing of Sildenafil as Hepatoprotective in Sinusoidal Obstruction Syndrome: Amendment of Endothelial Cell Damage and Inhibition of Platelet Aggregation". EKB Journal Management System, 1, 3, 2021, 21-31. doi: 10.21608/aijpms.2021.206681
Mansour, M., Gad, A., Zaky, H., Abdel Baky, N. (2021). 'Repurposing of Sildenafil as Hepatoprotective in Sinusoidal Obstruction Syndrome: Amendment of Endothelial Cell Damage and Inhibition of Platelet Aggregation', EKB Journal Management System, 1(3), pp. 21-31. doi: 10.21608/aijpms.2021.206681
Mansour, M., Gad, A., Zaky, H., Abdel Baky, N. Repurposing of Sildenafil as Hepatoprotective in Sinusoidal Obstruction Syndrome: Amendment of Endothelial Cell Damage and Inhibition of Platelet Aggregation. EKB Journal Management System, 2021; 1(3): 21-31. doi: 10.21608/aijpms.2021.206681

Repurposing of Sildenafil as Hepatoprotective in Sinusoidal Obstruction Syndrome: Amendment of Endothelial Cell Damage and Inhibition of Platelet Aggregation

Azhar International Journal of Pharmaceutical and Medical Sciences
Article 3, Volume 1, Issue 3, November 2021, Page 21-31  XML PDF (1.32 MB)
Document Type: Original research articles
DOI: 10.21608/aijpms.2021.206681
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Authors
Mona Mansour email orcid 1; Amany Gadorcid 2, 3; Heba Zakyorcid 1; Nayira Abdel Bakyorcid 1
1Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
2Department of Pharmacology, Egyptian Drug Authority (EDA), Formerly (NODCAR), Giza, Egypt
3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University (East Kantara Branch), New City, El Ismailia, Egypt.airo
Abstract
Hepatic sinusoidal obstructive syndrome (SOS) is a rare drug-induced fibrous occlusive hepatic entity. Up to now, there is no perfect therapy to avoid SOS, therefore, new curative options are clearly needed. The current research pointed to explore the probable protective effect of sildenafil against monocrotaline (MCT)-induced SOS, and to further identify the underlying mechanisms. Sildenafil was given to rats for 7 days orally (5 mg/kg/day). In the fourth day animals fasted, and given 90mg/kg MCT. Twenty-four hours after last dose of sildenafil administration, liver tissue and blood were collected to evaluate SOS. Results revealed that sildenafil amended oxidative stress in liver tissue as indicated by the significant increase in hepatic GSH level. Furthermore, sildenafil treatment significantly decreased the expression of liver sinusoidal endothelial cell injury markers (hyaluronic acid (HA), Vascular Cell Adhesion Molecule-1 (VCAM-1), and plasminogen activator inhibitor‐1(PAI-1), platelet aggregation markers (CD34, CD41 and P-selectin), as well as serum transaminases and hepatic caspase-3 activities. Additionally, macroscopic and histopathological examination of liver tissue augmented our biochemical findings. In conclusion, sildenafil markedly reversed the complicated and multifactorial pathophysiological state of SOS induced by MCT through its cytoprotective, thromboresistance effect on hepatic sinusoidal endothelial cells. Thereby, sildenafil proves to be a promising new therapeutic agent for SOS.
Keywords
Sinusoidal obstruction syndrome; monocrotaline; hepatic sinusoidal endothelial cell; Sildenafil; platelet aggregation
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