Cell lines

Human smooth muscle cells, human monocyte U937 cell line

Preparation method

The solubility of this compound in DMSO is >20.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

40 mg, 6 days

Applications

In human smooth muscle cells, addition of serum from patients (40 mg of fluvastatin a day for the 6 days) treated with fluvastatin caused a significant reduction in cell proliferation. Fluvastatin (100 nM) attenuated the expression of both ICAM-1 and LFA-1. Fluvastatin (10 μM) showed no effect on cell viability. Fluvastatin induced apoptosis in cardiac myocytes in a time- and dose-dependent manner. Fluvastatin decreased RhoA protein in the membrane fraction, whereas there were no significant changes of the RhoA protein in the cytosol fraction. Fluvastatin completely inhibited interleukin-1β-stimulated 3H-leucine incorporation.

Animal models

Sprague–Dawley male rats

Dosage form

Oral administration, 5, 10 and 20 mg/kg

Application

In hypercholesterolemic rats, treatment with fluvastatin (10 mg/kg/day) significantly attenuated the leukocyte-adherence responses to PAF and LTB4 as well as the leukocyte emigration response to LTB4. Fluvastatin treatment inhibited the PAF- and LTB4-induced reductions in leukocyte rolling velocity. Oral administration of fluvastatin (5, 10 and 20 mg/kg) significantly prevented almost all the parameters of isoproterenol-induced heart failure and myocardial injury. Compared with control group, any indexes in sham rats treated with fluvastatin (20 mg/kg) alone were unaltered. Treatment with fluvastatin resulted in a significant decrease in the urinary protein excretion. Fluvastatin treatment significantly ameliorated the decreased expression of nephrin in PAN nephrosis rats. Fluvastatin markly attenuated tubulointerstitial damage in the presence of moderate proteinuria.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Buemi M, Allegra A, Senatore M, et al. Pro-apoptotic effect of fluvastatin on human smooth muscle cells[J]. European journal of pharmacology, 1999, 370(2): 201-203.

[2]. Niwa S, Totsuka T, Hayashi S. Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line[J]. International journal of immunopharmacology, 1996, 18(11): 669-675.

[3]. Ogata Y, Takahashi M, Takeuchi K, et al. Fluvastatin induces apoptosis in rat neonatal cardiac myocytes: a possible mechanism of statin-attenuated cardiac hypertrophy[J]. Journal of cardiovascular pharmacology, 2002, 40(6): 907-915.

[4]. Zhou R, Xu Q, Zheng P, et al. Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat[J]. European journal of pharmacology, 2008, 586(1): 244-250.

[5]. Kimura M, Kurose I, Russell J, et al. Effects of fluvastatin on leukocyte–endothelial cell adhesion in hypercholesterolemic rats[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 1997, 17(8): 1521-1526.

[6]. Shibata S, Nagase M, Fujita T. Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling[J]. Journal of the American Society of Nephrology, 2006, 17(3): 754-764.