Effect of simvastatin on intestinal recovery following gut ischemia-reperfusion injury in a rat.
BACKGROUND
Pleiotropic (lipid lowering-independent) effects of statins are attributed to their antiinflammatory, antioxidant, and/or vascular actions. Extensive studies in various experimental models have established that pretreatment with simvastatin significantly protects heart and kidney injured by ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of simvastatin on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.


METHODS
Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (3) IR-SIM rats underwent IR and were treated with oral simvastatin (10 mg/kg) given by gavage immediately before and 24 h after operation. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P less than 0.05 considered statistically significant.


RESULTS
Treatment with simvastatin resulted in a significant increase in bowel and mucosal weight in ileum, villus height and crypt depth in jejunum and ileum compared to IR animals. IR-SIM rats had also a significantly lower intestinal injury score as well as lower apoptotic index in jejunum and ileum compared to IR animals.


CONCLUSIONS
Treatment with simvastatin prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Nadav
N
Slijper
Igor
I
Sukhotnik
Elena
E
Chemodanov
Yulia
Y
Bashenko
Ron
R
Shaoul
Arnold G
AG
Coran
Jorge
J
Mogilner
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin