Abstract
Purpose::
Statins which are HMG-CoA reductase inhibitors, form a class of hypolipidemic agents, used to lower cholesterol levels. Main adverse effects are myopathy and lethal rhabdomyolysis (breakdown of skeletal muscle). Besides, statins can induce cataract in some cases but studies are controversial about this issue. The aim of our study was to evaluate the effects of two statins on lens cells.
Methods::
Simvastatin and fluvastatin were incubated on a human lens cell line (SRA01/04) for 24h. Membrane integrity (necrosis), P2X7 cell death receptor activation (apoptosis) and oxidative stress (reactive oxygen species ROS and superoxide anion production O2.-) were evaluated using the neutral red, the YO-PRO-1, the DHCF-DA and the dihydroethidium tests. Tests were performed with cytofluorometry adapted to microplate.
Results::
At 10µm, simvastatin induced necrosis, apoptosis and oxidative stress (ROS and O2.-), whereas fluvastatin only induced apoptosis with a light ROS overproduction (at 1µM). On the one hand, simvastin, at weak concentration, induced hormesis effect which could explain the protective effect of statins against cataract observed in clinics. On the other hand, higher doses or long-term treatments could lead to cataract formation.
Conclusions::
As statins are prescribed to many patients, ocular side effects should be taken into account. An ophthalmic follow-up could avoid cataract.
Keywords: apoptosis/cell death • oxidation/oxidative or free radical damage • cataract