Fluvastatin pretreatment in mice significantly improved left ventricular function, including an 87% increase in cardiac output (P<0.05), attenuating doxorubicin-induced cardiotoxicity.
Does fluvastatin pretreatment attenuate doxorubicin-induced cardiotoxicity in mice?
Fluvastatin pretreatment attenuates doxorubicin-induced cardiotoxicity and improves LV function in mice via antioxidative and anti-inflammatory effects.
p-value: p=<0.05
Cardiotoxicity, which may result from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anticancer therapy using doxorubicin. Because statins might exert beneficial pleiotropic cardiovascular effects, among other things, by anti-inflammatory and antioxidative mechanisms, we investigated whether or not fluvastatin pretreatment can attenuate doxorubicin-induced cardiotoxicity. Five days after a single injection of doxorubicin (20 mg/kg; i.p.), left ventricular (LV) function was measured in fluvastatin-treated (DoxStatin; 100 mg/kg/day, p.o.) and saline-treated (doxorubicin) mice (n = 8 per group) by a micro conductance catheter. Untreated mice served as controls (placebo; n = 8 per group). After measurement of cardiac function, LV tissues were analyzed by molecular biological and immunohistologic methods. Injection resulted in significantly impaired LV function (LV pressure, -29%; dp/dtmax, -45%; cardiac output, -68%; P < 0.05) when compared with placebo. This was associated with a significant increase in cardiac oxidative stress, inflammation and apoptotic mechanisms, as indicated by significant increased cardiac lipid peroxidation activity, protein expression of nitrotyrosine, tumor necrosis factor alpha and Bax (P < 0.05). In contrast, DoxStatin mice showed improved LV function (LV pressure, +24%; dp/dtmax, +87%; cardiac output, +87%; P < 0.05) when compared with untreated doxorubicin mice. This was associated with reduced cardiac expression of nitrotyrosine, enhanced expression of the mitochondrial located antioxidative SOD 2, attenuated mitochondrial apoptotic pathways, and reduced cardiac inflammatory response. Statin pretreatment attenuates doxorubicin-induced cardiotoxicity via antioxidative and anti-inflammatory effects.
Riad et al. (Thu,) conducted a other in Doxorubicin-induced cardiotoxicity (n=24). Fluvastatin vs. Saline (doxorubicin alone) and untreated controls was evaluated on Left ventricular function (LV pressure, dp/dtmax, cardiac output) (p=<0.05). Fluvastatin pretreatment in mice significantly improved left ventricular function, including an 87% increase in cardiac output (P<0.05), attenuating doxorubicin-induced cardiotoxicity.