pitavastatin and Reperfusion-Injury

Statins (3-hydroxy-methylglutaryl coenzyme A reductase inhibitors) have been shown to lower serum cholesterol levels in clinical use. Moreover, it has been reported that statins exert pleiotropic and beneficial effects on vascular endothelium. Therefore, we investigated the effects of pitavastatin, a new statin, on leukocyte accumulation during ischemia-reperfusion injury.. Transient retinal ischemia was induced in Long-Evans rats for 60 min by temporal ligation of the optic nerve. Pitavastatin (0.12, 0.35, or 1.1 mg/kg) was administered 5 min prior to the induction of retinal ischemia. Leukocyte-endothelial interactions in the post-ischemic retina were evaluated in vivo with acridine orange digital fluorography. The number of rolling leukocytes, number of accumulated leukocytes, and diameters of the major retinal artery and vein were evaluated. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression in the retina was semiquantitatively studied using the RT-PCR method.. Pitavastatin-treated rats at doses of 0.35 and 1.1 mg/kg showed mild arterial narrowing (p < 0.01) and venous dilation (p < 0.01) compared with vehicle-treated (ischemic) rats. In rats treated with 0.35 mg/kg pitavastatin, the number of rolling leukocytes was significantly reduced by 35.5% (p < 0.01) 12 hr after reperfusion compared with that of vehicle-treated rats. With treatment at a dose of 0.35 mg/kg pitavastatin, the number of accumulated leukocytes was reduced to 68.7% (p < 0.01) 24 hr after reperfusion. Moreover, pitavastatin treatment significantly reduced ICAM-1 mRNA expression in the retina during ischemia-reperfusion injury.. Pitavastatin effectively attenuated ischemia-induced leukocyte-endothelial interactions in the rat retina.

Topics: Acridine Orange; Animals; Cell Communication; Endothelium, Vascular; Enzyme Inhibitors; Fluorescent Dyes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Leukocytes; Male; Quinolines; Rats; Rats, Long-Evans; Reperfusion Injury; Retinal Diseases; Retinal Vessels; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Atherosclerosis with hypoadiponectinemia can be further aggravated by intestinal ischemia/reperfusion (II/R)-induced injuries, such as bacterial translocation and lung injury. We investigated the effect of statin administration on the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.. Wistar rats were divided into 4 groups: (1) the Normal group (normal diet), (2) the Chol group (2% high cholesterol diet), (3) the St-1w group, and (4) the St-2w group (Chol group plus pitavastatin administration for 1 or 2 weeks, respectively). The serum concentrations of lipids and adiponectin were measured preoperatively. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 min, followed by 360 min of reperfusion (T1). Intestinal and lung nitric oxide (NO) concentrations were measured. Intestinal injury was assessed by microcirculatory flow, histology, and permeability. Bacterial translocation was assessed by analysis of serum peptidoglycan concentration. Lung injury was assessed by histologic examination, pulmonary permeability index, and wet/dry lung weight ratio.. The 2-week administration of statins with high-cholesterol feeding (St-2w group) improved hypoadiponectinemia to levels similar to those of the Normal group. Intestinal and lung NO concentrations were significantly lower at T1 in the Normal and St-2w groups than in the Chol group. Statin administration improved poor recovery of intestinal microcirculatory flow in the Chol group. At T1, intestinal and lung injuries were significantly aggravated and serum peptidoglycan concentration was significantly elevated in the Chol group compared with the Normal and St-2w groups. The 1-week administration of statins had no significant influence on serum adiponectin levels, tissue NO concentration, or tissue injury.. Administration of pitavastatin reduces the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia by improving hypoadiponectinemia and inhibiting inducible NO synthase-produced NO. Furthermore, preoperative improvement of hypoadiponectinemia may be important as an index of the protective effect of pitavastatin for II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.

Topics: Adiponectin; Animals; Atherosclerosis; Bacterial Translocation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intestinal Diseases; Lung Injury; Male; Nitric Oxide; Peptidoglycan; Quinolines; Rats; Rats, Wistar; Reperfusion Injury

To evaluate the neuroprotective effects of pitavastatin against neuronal retinal damage induced by ischemia-reperfusion injury in rats.. Ischemia-reperfusion injury was induced in Sprague-Dawley rats using ocular hypertension. Pitavastatin (0.1, 0.5, or 1.0 mg/kg) was given intravenously 12 hr or 5 min before, or 12 or 24 hr after the induction of ischemia-reperfusion injury. Morphometric and retrograde labeling analyses revealed neuroprotective effects when pitavastatin (0.5 mg/kg) was administered 5 min before--even 12 and 24 hr--after induction of ischemia-reperfusion injury. These effects depended on dose; protection was noted at pitavastatin concentrations of 0.5 and 1 mg/kg but not 0.1 mg/kg. Furthermore, preadministration of pitavastatin (0.5 mg/kg) reduced expression of P-selectin and intercellular adhesion molecule-1 at 12 and 24 hr after induction of ischemia-reperfusion injury.. As pitavastatin was efficacious in preventing retinal neuronal death, it may be a novel therapeutic modality for ischemic retinal diseases.

Topics: Animals; Cell Survival; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Injections, Intravenous; Intercellular Adhesion Molecule-1; Male; Neuroprotective Agents; P-Selectin; Quinolines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors