Inhibitory effect of statins on fetal bovine serum-induced proliferation of rat cultured mesangial cells and correlation between their inhibitory effect and transport characteristics.
Mesangial cells play an important role in physiologic functions, including the regulation of glomerular filtration, and as a pathogenic factor for proliferative glomerulonephritis. We compared the potencies of the inhibitory effects of simvastatin acid, lovastatin acid, and pravastatin on fetal bovine serum (FBS)-induced proliferation of rat cultured mesangial cells, and examined the correlation between their inhibitory effects and intracellular concentrations. We also investigated the transport of the statins in the cells, and whether or not their intracellular concentrations were determined by their transport characteristics. It appeared that the growth inhibitory effects on FBS-induced proliferation of mesangial cells of simvastatin acid and lovastatin acid were approximately the same, but that of pravastatin was extremely weak compared with the others. The growth inhibitory effects of these agents were suggested to depend, at least in part, on the amount incorporated intracellularly. Simvastatin acid, lovastatin acid, and pravastatin appeared to be taken up by mesangial cells via a common carrier, the uptake capacity being determined by their lipophilicity. Therefore, it was thought that the growth inhibitory effects of the statins partially depended on their carrier-mediated uptake by mesangial cells.
Nagasawa
K
K
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, 5, Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto, Japan. nagasawa@mb.kyoto-phu.ac.jp
Muraki
Y
Y
Matsuda
T
T
Ohnishi
N
N
Yokoyama
T
T
D000818:Animals; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D005312:Fetal Blood / Q000737:chemistry*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology*; D013696:Temperature
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012710:Serum Albumin, Bovine; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin