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.

Fluvastatin (XU 62-320 free acid) is a first fully synthetic, competitive HMG-CoA reductase inhibitor with an IC50 of 8 nM. Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway[1][2][3].

Fluvastatin (XU 62-320 free acid) is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMGCR), the enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Human hepatocellular carcinoma cell (HCC) studies indicate that Fluvastatin induces G2/M phase arrest. In the presence of Fluvastatin (XU 62320), HCC cells show a decrease of Bcl-2 and procaspase-9 expression, and an increase in Bax, cleaved caspase-3, and cytochrome c. Fluvastatin (XU 62320) is antilipemic and is used to reduce plasma cholesterol levels and prevent cardiovascular disease.

References:
[1]. Araújo FA, Rocha MA, Capettini LS, et al. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (fluvastatin) decreases inflammatory angiogenesis in mice. APMIS. 2012 24. [Epub ahead of print]
[2]. Makabe S, Takahashi Y, Watanabe H, et al. Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway. Atherosclerosis. 2010 Dec;213(2):377-84.
[3]. Zhang W, Wu J, Zhou L, et al. Fluvastatin, a lipophilic statin, induces apoptosis in human hepatocellular carcinoma cells through mitochondria-operated pathway. Indian J Exp Biol. 2010 Dec;48(12):1167-74.
[4]. Scripture CD, Pieper JA. Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001;40(4):263-81.