Eur J Anat, 23 (5): 325-332 (2019)

Liver ischemia/reperfusion injury, a setting in which the functional mass is reduced and the role of PDE5 inhibitor

Hesham N. Mustafa¹, Gehan A. Hegazy^2,3, Sally A. El Awdan⁴, Aliaa Amr Alamoudi²

¹Anatomy Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA, ²Clinical Biochemistry Depart-ment, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA, ³Medical Biochemistry Department, National Re-search Centre, Cairo, Egypt, ⁴Pharmacology Department, National Research Centre, Cairo, Egypt

ABSTRACT Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.

Keywords: Ischemia/reperfusion injury â?? Oxidati-ve stress â?? Apoptosis â?? TNF-α â?? BCL-2