Cell lines

J-774 A.1 macrophage-like cells, human monocyte derived macrophages (HMDM) and mouse peritoneal macrophages (MPM)

Preparation method

The solubility of this compound in DMSO is >13.2 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

0 ~ 100 μg/mL; 5 hrs

Applications

In J-774 A.1 macrophage-like cells, HMDM and MPM, Pravastatin Sodium reduced cholesterol biosynthesis in a dose-dependent manner, with the IC50 values of 0.08 μg/mL, 6.3 μg/mL and 7.8 μg/mL, respectively. In J-774 A.1 macrophage-like cells, Pravastatin Sodium increased degradation of low density lipoprotein (LDL), but not degradation of acetyl LDL and oxidized LDL.

Animal models

Otsuka Long-Evans Tokushima Fatty (OLETF) rats

Dosage form

100 mg/kg/day; p.o.; for 8 weeks

Applications

In OLETF rats, Pravastatin Sodium slightly reduced the fasting blood glucose level. However, Pravastatin Sodium significantly reduced superoxide production of vascular wall. In addition, Pravastatin Sodium normalized the level of serum glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs).

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.

Pravastatin sodium is a high selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase of 44.1nM [1].

Pravastatin is a competitive inhibitor of HMG-CoA reductase. It has shown to reduce the level of plasma LDL both in animals and humans through inhibiting cellular cholesterol synthesis. Pravastatin was reported to reduce cellular cholesterol synthesis in three types of macrophages including J-774 A.1 macrophage-like cell line, human monocyte derived macrophages (HMDM) and mouse peritoneal macrophages (MPM) with IC50 values of 0.08, 6.3 and 7.8μg/ml, respectively [2].

Besides the benefit in cardiovascular disease prevention, pravastatin also has efficacy of preventing tumor growth in some degree. However, it has shown that the normal hepatocytes are more sensitive to pravastatin than the tumor cells since pravastatin is selectively taken up by OATP1B1 which is exclusively expressed in normal hepatocytes [3].

References:
[1] Bolego C, Poli A, Cignarella A, Catapano AL, Paoletti R. Novel statins: pharmacological and clinical results. Cardiovasc Drugs Ther. 2002 May;16(3):251-7.
[2] Keidar S, Aviram M, Maor I, Oiknine J, Brook JG. Pravastatin inhibits cellular cholesterol synthesis and increases low density lipoprotein receptor activity in macrophages: in vitro and in vivo studies. Br J Clin Pharmacol. 1994 Dec;38(6):513-9.
[3] Menter DG, Ramsauer VP, Harirforoosh S, Chakraborty K, Yang P, Hsi L, Newman RA, Krishnan K. Differential effects of pravastatin and simvastatin on the growth of tumor cells from different organ sites. PLoS One. 2011;6(12):e28813.