Cerivastatin does not prevent oxidative injury of human aortic endothelial cells.
The anti-atherogenic properties of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been well established in several circulatory beds. Increasing evidence suggests that statins may help attenuate ischemia-reperfusion injury, a beneficial effect that may be related to the antioxidant capabilities of statins; however, this remains controversial. We performed this study to determine whether the HMG-CoA reductase inhibitor cerivastatin can prevent oxidative stress-induced injury in cultured human aortic endothelial cells (HAEC). The HAEC were subjected to oxidative stress in the absence and presence of increasing concentrations of cerivastatin (50 nM-1,000 nM). Oxidative stress was induced by increasing concentrations of hydrogen peroxide or endogenous superoxide anions generated by the inhibition of superoxide dismutase using diethylthiocarbamate (10 mM). Cell viability and mitochondrial activity were measured by mitochondria-dependent 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) conversion. Cell morphology was also examined using light microscopy. Exposing HAEC to cerivastatin for 24 hours had no effect on cell viability using both cell morphology and MTT conversion: the HAEC incubated in 100 nM cerivastatin had 90% +/- 2.2% viability of the control. As expected, hydrogen peroxide produced a concentration-dependent decrease in cell viability. Varying concentrations of cerivastatin pretreatment for < or = 18 hours showed no protection of HAEC against hydrogen peroxide-induced injury. As a positive control, the prototype antioxidant N-acetyl-L-cysteine was cytoprotective even with the highest hydrogen peroxide concentration. Neither cerivastatin nor N-acetyl-L-cysteine protected HAEC against diethylthiocarbamate-induced oxidative injury at any concentration. In this study, cerivastatin did not protect cultured HAEC against oxidative stress induced by hydrogen peroxide or diethylthiocarbamate.
Al-Ruzzeh
Sharif
S
Department of Cardiothoracic Surgery, Harefield Hospital, Middlesex UB9 6JH, United Kingdom.
Schmidt
Ilona
I
Nakamura
Koki
K
Chester
Adrian
A
Ilsley
Charles
C
Amrani
Mohamed
M
D001011:Aorta / Q000187:drug effects* / Q000293:injuries; D004727:Endothelium / Q000187:drug effects* / Q000293:injuries; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin