کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2580596 | 1561634 | 2014 | 9 صفحه PDF | دانلود رایگان |
• Apocynin has a potential role in reducing the cardiotoxicity of cisplatin.
• It notably ameliorated the state of oxidative stress and mitigated inflammation.
• It inhibited Nrf2, HO-1 and NF-κB overexpressions.
• It preserved mitochondrial membrane potential.
• It reduced elevated caspase-3 activity and nuclear DNA fragmentation.
Despite the clinical reports, few studies have focused on reducing the cardiotoxicity of cisplatin. In the present study, cardiotoxicity was examined after a single ip injection of cisplatin (7 mg/kg) in rats. Apocynin was given in drinking water (600 mg/L) for five successive days before and after cisplatin injection. At the end of the experiment, hemodynamic parameters were recorded, animals were sacrificed and serum creatine kinase-MB activity was determined. The whole ventricle was isolated for estimation of tumor necrosis factor-alpha (TNF-α) content, NADPH oxidase, myeloperoxidase and caspase-3 activities in addition to nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nuclear factor kappa B (NF-κB) gene expressions. Furthermore, oxidative stress markers and antioxidant enzymes were measured in postmitochondrial and mitochondrial fractions. Mitochondrial membrane potential, nuclear DNA fragmentation and cardiomyocyte cross-sectional area were also evaluated. Apocynin was effective against cisplatin-induced decrement in heart rate and blood pressure. Moreover, pretreatment with apocynin notably ameliorated the state of oxidative stress, mitigated inflammation and preserved mitochondrial membrane potential. Apocynin provided also a significant cardioprotection as revealed by alleviating the overexpression of Nrf2, HO-1 and NF-κB, the elevation of caspase-3 activity, the prominent nuclear DNA fragmentation and the decreased cardiomyocyte cross-sectional area. This study highlights the potential role of apocynin in inhibiting cisplatin-induced hemodynamic changes, postmitochondrial and mitochondrial damage as indicated by improvement in the state of oxidative stress, inflammation and apoptosis.
Figure optionsDownload as PowerPoint slide
Journal: Chemico-Biological Interactions - Volume 207, 25 January 2014, Pages 58–66