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 TNFα 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

Simvastatin attenuates intestinal ischaemia/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-&#945;, 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 goup, 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-&#945; 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-&#945; and tissue malondealdehyde level, and simvastatin administration maintained cellular antioxidant enzyme contents compared to the I/R group after 3 hours reperfusion time

Mechanical versus thermodynamical melting in pressure-induced amorphization: the role of defects

We study numerically an atomistic model which is shown to exhibit a one--step crystal--to--amorphous transition upon decompression. The amorphous phase cannot be distinguished from the one obtained by quenching from the melt. For a perfectly crystalline starting sample, the transition occurs at a pressure at which a shear phonon mode destabilizes, and triggers a cascade process leading to the amorphous state. When defects are present, the nucleation barrier is greatly reduced and the transformation occurs very close to the extrapolation of the melting line to low temperatures. In this last case, the transition is not anticipated by the softening of any phonon mode. Our observations reconcile different claims in the literature about the underlying mechanism of pressure amorphization.Comment: 7 pages, 7 figure

Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats

Background: Pulmonary fibrosis induced by paraquat (PQ) has caused a large number of human fatalities all over the world, especially in Asian region. The main potential mechanism of PQ toxicity has been thought to be mediated by ROS. The present study was designed to evaluate the efficacy of the Berberis vulgaris fruit extract (BVFE) against PQ-induced pulmonary fibrosis in rats. Methods: Forty male rats were randomly divided into five experimental groups each containing eight rats. Groups 1 and 2, served as a negative and positive control and received a single dose of intratracheal instillation of saline and PQ (20 mg/kg), respectively. Groups 3-5 were treated with different doses of BVFE (100, 200, 400 mg/kg/day, orally) 1 week before the PQ injection and continued for 3 weeks. The rats were sacrificed 21 days after PQ. Malondialdehyde (MDA), Hydroxyproline, inflammatory and fibrogenic cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-β1 in lung tissue were determined. Presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in lung were evaluated microscopically by hematoxylin and eosin (H&E) staining. Dried extract was standardized by amount of berberine by HPTLC methods by silica gel plate. Results: The results showed that PQ could significantly increase the lung MDA, hydroxyproline, TNF-α, IL-6 and TGF-β1 levels. BVFE ameliorated the biochemical and histological lung alterations induced by PQ. Conclusions: The present study indicates the hydroalcolic extract of Berberis vulgaris fruit has beneficial effects in rat pulmonary fibrosis induced by PQ in a dose-dependent manner, possibly by anti-oxidant and anti- inflammatory properties, which might be due to its berberine alkaloid content. © 2016 Elsevier Masson SAS