L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes

Chao, Hung-Hsing; Liu, Ju Chi; Hong, Hong Jye; Lin, Jia Wei; Chen, Cheng Hsien; Cheng, Tzu-Hurng

doi:10.1016/j.ijcard.2009.06.010

Cited by 48 publications

(27 citation statements)

References 42 publications

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“…Hesperetin treatment along with DOX treatment prevented the DNA damage in the heart nuclei as evident from the evaluation of various comet assay parameters. DOX has been reported to induce apoptosis in rat heart [37]. Apoptotic effect of DOX was made evident in the present study by halo assay and TUNEL assay, which substantiates the cytotoxic effect of DOX on cardiomyocytes [33].…”

Section: Discussionsupporting

confidence: 87%

Cardioprotective Effects of Hesperetin against Doxorubicin-Induced Oxidative Stress and DNA Damage in Rat

et al. 2011

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Doxorubicin is a widely used chemotherapeutic agent; however, its clinical uses are limited due to its cardiotoxicity associated with an induction of oxidative stress. This study was aimed to investigate the protective effect of hesperetin against doxorubicin-induced cardiotoxicity in rats. Doxorubicin was administered at the dosage of 4 mg/kg bw/week, ip for a period of 5 consecutive weeks. Hesperetin was administered at the dosages of 25, 50 and 100 mg/kg bw, po by gavage for 5 consecutive days in a week for 5 weeks. The animals were killed 1 week after the last injection of doxorubicin. Hesperetin at the doses of 50 and 100 mg/kg bw significantly reduced MDA and increased GSH levels in the doxorubicin-treated animals. Further, hesperetin significantly reduced doxorubicin-induced DNA damage as well as apoptosis at 25, 50, and 100 mg/kg bw as evident from the comet and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assays, respectively. Thus, hesperetin ameliorated doxorubicin-induced cardiotoxicity by reducing oxidative stress, abnormal cellular morphology and DNA damage in rat. Moreover, nuclear factor-kappa B, p38, and caspase-3 play a role in the hesperetin-mediated protection against doxorubicin-induced cardiotoxicity. This study indicates the protective effect of hesperetin against doxorubicin-induced cardiotoxicity.

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Section: Discussionsupporting

confidence: 87%

Cardioprotective Effects of Hesperetin against Doxorubicin-Induced Oxidative Stress and DNA Damage in Rat

et al. 2011

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“…Overexpression of p300 protects cardiac myocytes from doxorubicin-induced apoptosis by increasing the cardiac level of bcl-2 and mdm-2 [30]. Lcarnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes [151]. Nuclear calcium/calmodulindependent protein kinase IIdeltaB (CaMKIIdeltaB) is required for GATA-4-mediated co-activation and binding to the Bcl-2 promoter.…”

Section: Preventionmentioning

confidence: 99%

Mechanisms and management of doxorubicin cardiotoxicity

Shi

Moon

Dawood

et al. 2011

Herz

186

133

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Doxorubicin is an effective anti-tumor agent with a cumulative dose-dependent cardiotoxicity. In addition to its principal toxic mechanisms involving iron and redox reactions, recent studies have described new mechanisms of doxorubicin-induced cell death, including abnormal protein processing, hyper-activated innate immune responses, inhibition of neuregulin-1 (NRG1)/ErbB(HER) signalling, impaired progenitor cell renewal/cardiac repair, and decreased vasculogenesis. Although multiple mechanisms involved in doxorubicin cardiotoxicity have been studied, there is presently no clinically proven treatment established for doxorubicin cardiomyopathy. Iron chelator dexrazoxane, angiotensin converting enzyme (ACE) inhibitors, and β-blockade have been proposed as potential preventive strategies for doxorubicin cardiotoxicity. Novel approaches such as anti-miR-146 or recombinant NRG1 to increase cardiomyocyte resistance to toxicity may be of interest in the future.

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“…Western blot analysis was performed as previously described [14] . Membranes were blocked in 10 mmol/L Tris (pH 7.5), 100 mmol/L NaCl, and 0.1% Tween 20 containing 5% nonfat dry milk, followed by incubation with the primary antibody.…”

Section: Western Blot Analysismentioning

confidence: 99%

Tanshinone IIA attenuates angiotensin II-induced apoptosis via Akt pathway in neonatal rat cardiomyocytes

Hong

Liu²,

Cheng

et al. 2010

Acta Pharmacol Sin

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Aim: To examine the effects of tanshinone IIA, the main effective component of Salvia miltiorrhiza (known as 'Danshen' in traditional Chinese medicine) on angiotensin II (Ang II)-mediated cardiomyocyte apoptosis. Methods: Rat neonatal cardiomyocytes were primarily cultured with Ang II or Ang II plus tanshinone IIA. Myocyte apoptosis was evaluated by caspase-3 activity and DNA strand break level with TdT-mediated dUTP nick-end labeling (TUNEL) staining. Western blot analysis was employed to determine the related protein expression and flow cytometry assay was used to determine the TUNEL positive cells and the intracellular reactive oxygen species (ROS) production. SiRNA targeted to Akt was used. Results: Ang II (0.1 µmol/L) remarkably increased caspase-3 activity, TUNEL positive cells, and cleaved caspase-3 and cytochrome c expression, but reduced Bcl-X L expression. These effects were effectively antagonized by pretreatment with tanshione IIA (1−3 µmol/L). Tanshinone IIA had no effect on basal ROS level, while attenuated the ROS production by Ang II. Interestingly, tanshione IIA significantly increased the phosphorylated Akt level, which was countered by the PI3K antagonist wortmannin or LY294002. Knockdown of Akt with Akt siRNA significantly reduced Akt protein levels and tanshinone IIA protective effect. Conclusion: Tanshinone IIA prevents Ang II-induced apoptosis, thereby suggesting that tanshinone IIA may be used for the prevention of the cardiac remodeling process.

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L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes

Cited by 48 publications

References 42 publications

Cardioprotective Effects of Hesperetin against Doxorubicin-Induced Oxidative Stress and DNA Damage in Rat

Cardioprotective Effects of Hesperetin against Doxorubicin-Induced Oxidative Stress and DNA Damage in Rat

Mechanisms and management of doxorubicin cardiotoxicity

Tanshinone IIA attenuates angiotensin II-induced apoptosis via Akt pathway in neonatal rat cardiomyocytes

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