4-hydroxy-2-nonenal and pitavastatin

We have reported previously that intermittent hypoxia related to sleep apnea induces cardiovascular remodeling secondary to the oxidative stress. The aim of this study was to examine the effect of pitavastatin as an antioxidant to prevent intermittent hypoxia-induced left ventricular (LV) remodeling in mice without hypercholesterolemia. Eight-week-old male C57BL/6J mice (n=35) were exposed to intermittent hypoxia (30 s exposure to 5% oxygen, followed by 30 s exposure to 21% oxygen) for 8 h per day during the daytime or maintained under normoxic conditions; in addition, they were either treated with pitavastatin (3 mg kg(-1) per day) or vehicle for 10 days. After cardiac catheterization and blood sampling, the LV myocardium was examined. The systemic blood pressure and plasma level of total cholesterol were similar among the four groups. Intermittent hypoxia significantly increased the expression levels of 4-hydroxy-2-nonenal (4-HNE) proteins, TNF-alpha and TGF-beta mRNA, and also the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL)-positive myocardial cells in the LV myocardium. In addition, enhanced hypertrophy of the cardiomyocytes, perivascular fibrosis and histological degeneration were observed in the mice exposed to hypoxic stress. Treatment with pitavastatin significantly suppressed the expression levels of the 4-HNE proteins, cytokines, superoxide production and TUNEL-positive myocardial cells in the LV myocardium, consequently attenuating the hypoxia-induced histological changes. Pitavastatin preserved, at least partially, the morphological structure of the LV myocardium in lean mice exposed to intermittent hypoxia, through its antioxidant effect.

Topics: Aldehydes; Animals; Antioxidants; Blood Pressure; Cholesterol; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoxia; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred C57BL; Myocardium; Oxidative Stress; Quinolines; Sleep Apnea Syndromes; Thinness; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Ventricular Remodeling

This study aimed to clarify the effect of statins on spontaneous stroke and to examine the antioxidative effect in artificial transient middle cerebral artery occlusion (tMCAO).. Stroke-prone spontaneous hypertensive rats (SHR-SP) were treated with pitavastatin, atorvastatin, simvastatin, or vehicle for 4 weeks. Physiological parameters, serum lipids, and infarct volumes were examined. The markers for oxidative stresses on lipids and DNA were immunohistochemically detected in vehicle-treated or simvastatin-treated SHR-SP with tMCAO.. Atorvastatin and simvastatin decreased infarct volumes, with simvastatin most effective. Simvastatin significantly reduced immunoreactivities for oxidative stress markers for lipids and DNA in neurons after tMCAO.. The results suggest that the antioxidative properties of statins may be implicated in their beneficial effects against neuronal damage in cerebral ischemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Atorvastatin; Blood Pressure; Body Weight; Deoxyguanosine; Disease Models, Animal; Heptanoic Acids; Hydroxymethylglutaryl CoA Reductases; Infarction, Middle Cerebral Artery; Lipids; Lysine; Oxidative Stress; Pyrroles; Quinolines; Rats; Rats, Inbred SHR; Simvastatin; Survival Analysis