Simvastatin attenuates intestinal ischemia/reperfusion induced injury in rat

Folia Morphol (Warsz). 2009 Aug;68(3):156-62.

Abstract

Ischaemia/reperfusion (I/R) injury is commonly seen in the field of intestine surgical interventions, shock, trauma, and many other clinical conditions. Simvastatin is known to have antioxidant and anti-inflammatory properties. This study investigated the effect of simvastatin administration in a warm intestinal I/R model on TNF-alpha, antioxidant enzymes and intestinal tissue morphology. Thirty-six male wistar rats underwent laparotomy under general anaesthesia. Simvastatin was administered from four days before ischaemia induction. The rats were divided in to three groups (n = 12): the sham group, the I/R group, and the I/R + simvastatin group. Intestinal ischaemia was induced by superior mesenteric artery ligation with microvascular clamps for 60 minutes, and after ischaemia, blood perfusion was released into the tissue and a reperfusion phase was started, which lasted for 3 hours. After 3 hours, the animals were sacrificed and serum and tissue obtained for biochemical and histological study. In the simvastatin treated group, intestinal tissue injury, TNF-alpha level, and tissue malondealdehyde levels were significantly lower than in the I/R group (p < 0.05). Glutathion peroxidase and superoxide dismutase levels were significantly higher in the simvastatin treated group than in the I/R group (p < 0.05). Simvastatin pretreatment reduced intestinal I/R injury and was associated with down- -regulation of serum TNF-alpha and tissue malondealdehyde level, and simvastatin administration maintained cellular antioxidant enzyme contents compared to the I/R group after 3 hours reperfusion time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Free Radical Scavengers / metabolism
  • Glutathione / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Intestinal Diseases / drug therapy*
  • Intestinal Diseases / metabolism
  • Intestinal Diseases / physiopathology
  • Ischemia / drug therapy*
  • Ischemia / metabolism
  • Ischemia / physiopathology
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Simvastatin / pharmacology*
  • Simvastatin / therapeutic use
  • Superoxide Dismutase / metabolism
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Simvastatin
  • Superoxide Dismutase
  • Glutathione