Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion Mustafa Inan a, ⁎ , Yesim Hulya Uz b , Gulnur Kizilay b , Yeter Topcu-Tarladacalisir b , Melike Sapmaz-Metin b , Meryem Akpolat c , Nurettin Aydogdu d a Department of Pediatric Surgery, Faculty of Medicine, Trakya University, Edirne, Turkey b Department of Histology and Embryology, Faculty of Medicine, Trakya University, Edirne, Turkey c Department of Histology and Embryology, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey d Department of Physiology, Faculty of Medicine, Trakya University, Edirne, Turkey Received 16 August 2012; revised 26 November 2012; accepted 25 December 2012 Key words: Sildenafil; Intestine; Ischemia-reperfusion; Liver; Intestinal ischemia/ reperfusion-induced liver injury Abstract Background: This study evaluated the protective effect of sildenafil on liver injury induced by intestinal ischemia-reperfusion. Methods: Forty female Sprague Dawley rats were divided into 4 groups: sham-control (SC), ischemia (I), ischemia-reperfusion (IR), and ischemia-reperfusion + sildenafil (SIL; sildenafil gavaged at 50 mg/kg before operating). A 2-h ischemia-reperfusion was performed by clamping the superior mesenteric artery. Liver function, plasma alanine (ALT) and aspartate (AST) aminotransferase, and intestinal and liver malondialdehyde (MDA) were measured at the end of the experiment. Intestinal and liver tissue damage was examined by histology. Liver samples were immunologically stained for endothelial nitric oxide synthase (eNOS) and proliferating cell nuclear antigen (PCNA). Results: The ALT and AST levels were highest in the IR group and were lower in the SIL group (p b 0.05). Intestinal MDA levels were statistically higher in the IR group than in the SC, I and SIL groups. Liver MDA levels were significantly higher in the IR group than in the I and SC groups (p b 0.05) and higher than in the SIL group (p N 0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p b 0.05). Sildenafil reduced damage and also increased eNOS and PCNA immunoreactivity in liver tissue. Conclusions: Sildenafil shows a protective effect on intestinal ischemia-reperfusion-induced liver injury, possibly by decreasing vascular resistance through increased nitric oxide levels. © 2013 Elsevier Inc. All rights reserved. Intestinal damage caused by ischemia-reperfusion (I/R) may occur for various reasons in all age groups but is particularly prevalent in infants and children who experience events such as incarcerated inguinal hernia, intussusception, midgut volvulus, hemorrhagic or traumatic shock, severe burns, sepsis, necrotizing enterocolitis, ischemic colitis, arterial thrombi and embolism, aortic or cardiac surgery, and liver or intestinal transplantation [1–4]. These life- threatening problems may be complicated by multiple organ failure, shock, and death [2]. The hepatic tissue is the first to sustain injury and represents a critical remote structure ⁎ Corresponding author. Trakya Universitesi, Tip Fakultesi, Cocuk Cerrahisi AD, 22030, Edirne-Turkey. Tel.: + 90 284 2357641; fax: + 90 284 2357652. E-mail address: mustafainan@trakya.edu.tr (M. Inan). www.elsevier.com/locate/jpedsurg 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2012.12.054 Journal of Pediatric Surgery (2013) 48, 1707–1715