Acute doxorubicin administration in rats impaired left ventricular fractional shortening (0.51 vs 0.59; p<0.001) and increased MMP-2 activity.
Does acute doxorubicin administration induce cardiac dysfunction and alter MMP-2 activity in Wistar rats?
Acute doxorubicin administration induces left ventricular dysfunction and increased myocardial passive stiffness in rats, associated with myocardial MMP-2 activation.
Tasa de eventos absoluta: 0.51% vs 0.59%
valor p: p=<0.001
BACKGROUND: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. METHODS: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. RESULTS: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 ± 0.07; Doxo 0.51 ± 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 ± 4.3; Doxo 24.7 ± 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 ± 8924; Doxo 188874 ± 7652 arbitrary units; p < 0.001). There were no changes in TNF-α, INF-γ, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. CONCLUSION: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.
Polegato et al. (Thu,) conducted a other in Doxorubicin-induced cardiotoxicity. Doxorubicin vs. Saline was evaluated on Left ventricular fractional shortening (p=<0.001). Acute doxorubicin administration in rats impaired left ventricular fractional shortening (0.51 vs 0.59; p<0.001) and increased MMP-2 activity.