title: Sildenafil attenuates hepatocellular injury after liver ischemia reperfusion in rats: a preliminary study.
abstract: We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect.
authors.affiliation: Experimental Surgical Unit, Aretaieion University Hospital, 11528 Athens, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Savvanis
authors.affiliation: Second Department of Surgery, Aretaieion University Hospital, 11528 Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Nastos
authors.affiliation: Second Department of Surgery, Aretaieion University Hospital, 11528 Athens, Greece.
authors.forename: Marios-Konstantinos
authors.initials: MK
authors.lastname: Tasoulis
authors.affiliation: Experimental Surgical Unit, Aretaieion University Hospital, 11528 Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papoutsidakis
authors.affiliation: Pathology Department, Sismanoglio General Hospital, 15126 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Demonakou
authors.affiliation: Department of Anesthesiology, Penteli Pediatric Hospital, 15236 Athens, Greece.
authors.forename: Iosifina
authors.initials: I
authors.lastname: Karmaniolou
authors.affiliation: Fourth Department of Surgery, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.affiliation: Fourth Department of Surgery, Attikon University Hospital, 12462 Athens, Greece.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Smyrniotis
authors.affiliation: Department of Anesthesiology, Aretaieion University Hospital, 11528 Athens, Greece.
authors.forename: Kassiani
authors.initials: K
authors.lastname: Theodoraki
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000473:pathology*; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology; D000068677:Sildenafil Citrate; D013194:Staining and Labeling; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D012333:RNA, Messenger; D013450:Sulfones; D018799:Intercellular Adhesion Molecule-1; D000068677:Sildenafil Citrate; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase