Simvastatin attenuates intestinal ischemia/reperfusion induced injury in rat.

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.

Simvastatin decreases hepatic ischaemia/reperfusion-induced liver and lung injury in rats.

Liver failure is still a significant clinical problem after transplantation surgery, tissue resections (the Pringle manoeuvre) and haemorrhagic shock. The restoration of blood flow to an ischaemic region leads to tissue injury at a greater rate than the original ischaemic insult, an event termed "ischaemia-reperfusion injury" (I/R). Despite advances in surgical techniques, I/R still poses a problem of clinical importance. In this research, we studied the effect of simvastatin pretreatment on liver and lung injury induced by hepatic I/R. Rats were subjected to 30 min of ischaemia followed by 24 h of reperfusion. Simvastatin (10 mg/kg) was administered orally from three days before the operation. After the reperfusion time, serum ALT, AST, LDH and TNF a levels were studied and liver and lung tissues were stained with haematoxylin and eosin and TUNEL to detect apoptotic cells. Serum aminotransferase activity and LDH and TNFalpha levels were increased markedly by hepatic I/R, and these were suppressed significantly by simvastatin. The tissue injury index and the number of apoptotic cells via TUNEL staining in the liver and lungs were higher in the I/R group than in the I/R + simvastatin group. These results suggest that simvastatin ameliorates I/R-induced liver and lung tissue damage by inhibiting the level of inflammation and the apoptotic pathways. Simvastatin administration may therefore provide protection against the adverse effects of I/R injury in liver transplantation.