The Controversy Around Callous Temozolomide-Methods

?2002; Liu?et al.?2004; Yue?et al.?2005; Tao?et al.?2010; Zhang?et al.?2010), suggesting that rosiglitazone has an anti-apoptotic effect in myocardium during ischaemia�Creperfusion. As mitochondrial ROS production is involved in cell apoptotic pathways (Loor?et al.?2011) and rosiglitazone could not prevent ROS production, our findings suggest that anti-apoptotic effect of rosiglitazone may not be direct, via the mitochondria, but that it could be involved in the extrinsic apoptotic signalling pathway, which is a mitochondria-independent apoptosis pathway that mediates cellular apoptosis by activating death receptors and transmiting apoptotic signals after ligation with specific ligands (Ashe & Berry, 2003; Delhalle?et al.?2003). However, the inflammatory response could also be responsible for the infarct size reduction observed in this study. Previous studies Temozolomide ic50 demonstrated that inflammation could play an important role in myocardial infarction during ischaemia�Creperfusion (Werns & Lucchesi, 1987; Bonvini?et al.?2005); therefore, inhibition of the inflammatory response might reduce Vismodegib solubility dmso myocardial infarct size (Werns & Lucchesi, 1987). As rosiglitazone has been shown to inhibit the inflammatory response by reducing the accumulation of neutrophils and macrophages and the expression of monocyte chemoattractant protein-1 (MCP-1) in the ischaemic heart (Yue?et al.?2001) and by inhibiting the inflammatory cytokines tumour necrosis factor-�� and nuclear factor-��B (Shah?et al.?2005), the infarct size reduction found in this study Moroxydine could be due to the anti-inflammatory effect of rosiglitazone. Future studies are required to elucidate the anti-apoptotic mechanism of rosiglitazone. Nevertheless, the controversy regarding the cardioprotective effect of rosiglitazone by its ability to decrease the infarct size (Sidell?et al.?2002; Liu?et al.?2004; Yue?et al.?2005; Tao?et al.?2010; Zhang?et al.?2010) and the increased mortality with its use (Lygate?et al.?2003; Lu?et al.?2008; Blasi?et al.?2009) have converged into the present study showing that rosiglitazone, despite its infarct size reduction effect, facilitates the occurrence of fatal arrhythmia during ischaemia�Creperfusion injury, and could be responsible for increased mortality in patients using this drug, as shown in clinical trials (Diamond?et al.?2007; Home?et al.?2007; Lipscombe?et al.?2007; Nissen & Wolski, 2007). In the present study, we did not assess the anti-inflammatory signalling, cardiac function or structural changes of cardiomyocytes. However, previous studies demonstrated that rosiglitazone could improve cardiac function during ischaemia�Creperfusion (Geng?et al.?2006; Gonon?et al.?2007), suggesting that rosiglitazone could influence cardiac function during ischaemia�Creperfusion injury. This work was supported by the Faculty of Medicine Endowment Fund (N.C. and S.P.) and grants from the Thailand Research Fund RTA 5280006 (N.C.