Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion.
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 50mg/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<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<0.05) and higher than in the SIL group (p>0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p<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.
Department of Pediatric Surgery, Faculty of Medicine, Trakya University, Edirne, Turkey. mustafainan@trakya.edu.tr
Mustafa
M
Inan
Yesim Hulya
YH
Uz
Gulnur
G
Kizilay
Yeter
Y
Topcu-Tarladacalisir
Melike
M
Sapmaz-Metin
Meryem
M
Akpolat
Nurettin
N
Aydogdu
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003250:Constriction; D004353:Drug Evaluation, Preclinical; D005260:Female; D007422:Intestines / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008112:Liver Glycogen / Q000032:analysis; D008315:Malondialdehyde / Q000032:analysis; D017538:Mesenteric Artery, Superior; D065666:Mesenteric Ischemia; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D011687:Purines / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D014652:Vascular Diseases / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D008112:Liver Glycogen; D010879:Piperazines; D018809:Proliferating Cell Nuclear Antigen; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D000068677:Sildenafil Citrate; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
Intestinal ischemia/reperfusion-induced liver injury; Intestine; Ischemia-reperfusion; Liver; Sildenafil