510 Effect of Grape Seeds Extract in the Modulation of Matrix Metalloproteinase-9 Activity and Oxidative Stress Induced By Doxorubicin in Mice

Abstract: The therapeutic value of doxorubicin as antitumor agent is limited by its cardiotoxicity. Matrix metalloproteinases activation is an early event in doxorubicin-induced cardiotoxicity. Because Matrix metalloproteinases are up-regulated by increased formation of reactive oxygen species, the present study was designed to tested whether the grape seeds extract could attenuate the increases in matrix metalloproteinase-9 activity and prevent the doxorubicin -induced cardiotoxicity in mice. Mice were dosed with a single injection of doxorubicin (20 mg/kg b.wt , i.p) with or without pretreatment of grape seeds extract. The protective role of grape seeds extract against doxorubicin induced-cardiac damage was evaluated on the aspects of the release of cardiac enzymes into serum, the formation of malondialdehyde, the activation of matrix metalloproteinase-9 and the histopathological changes in heart tissues. The results showed that doxorubicin led to increase in serum metalloproteinase-9 activity, heart injury as shown by increased serum creatine kinase, lactate dehydrogenase, alanin aminotranseferase and aspartat aminotransferase. Oxidative stress was also increased in cardiac tissue as shown by increased malondialdehyde and decrease of antioxidants (superoxide dismutase, catalase and reduced glutathione). This damage was accompanied with histopathological changes in the heart tissue. Pretreatment with GS extract (100mg/kg b.wt daily for 12 days) effectively hindered the adverse effect of doxorubicin and protect against cardiac damage via suppression of oxidative stress