Effects of pravastatin on superoxide and fibronectin production of mesangial cells induced by low-density lipoprotein.
Pravastatin is a potent inhibitor of HMG-CoA reductase and is effective in lowering serum lipid levels. Recent studies have shown that pravastatin also reduces the oxidative modification of low-density lipoprotein (LDL). To determine whether pravastatin has a direct effect on glomerular mesangial cells, we have measured the effects of pravastatin on the production of superoxide and fibronectin of glomerular mesangial cells stimulated by LDL. Our results demonstrated that the superoxide production of mesangial cells increased after LDL stimulation (100 microg/ml for 4 h) and that the superoxide production was significantly suppressed by either superoxide dismutase (SOD; 500 U/ml for 36 h; p < 0.01) or pravastatin (80 microM for 36 h; p < 0.05). The production of fibronectin was also increased after LDL stimulation which was also significantly suppressed by either SOD (p < 0.01) or pravastatin (p < 0.01). SOD or pravastatin alone had no effect on the unstimulated cells. Our results indicate that pravastatin may have a direct effect as an antioxidant and suppresses the fibronectin synthesis of glomerular mesangial cells independent of its hypolipidemic effect.
Chen
Hung-Chun
HC
Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Guh
Jinn-Yuh
JY
Shin
Shyi-Jang
SJ
Tomino
Yasuhiko
Y
Lai
Yung-Hsiung
YH
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009994:Osmolar Concentration; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D005353:Fibronectins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D013481:Superoxides; D017035:Pravastatin