Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following myocardial infarction in rat.

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Title: Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following myocardial infarction in rat.
Authors: Rivard AL (AUTHOR), Steer CJ (AUTHOR), Kren BT (AUTHOR), Rodrigues CMP (AUTHOR), Castro RE (AUTHOR), Bianco RW (AUTHOR), Low WC (AUTHOR)
Source: American Journal of Chinese Medicine. 2007, Vol. 35 Issue 2, p279-295. 17p.
Abstract: Black bear bile has been used in traditional Chinese medicine to treat liver and eye related illnesses for centuries. A major constituent of bile is ursodeoxycholic acid (UDCA). Recent analysis of the cellular effects of UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) have demonstrated their antiapoptotic properties through regulation of Bcl-2 family and survival signaling proteins (Bax, Bad, phosphatidylinositol-3-kinase). In this study, we tested the hypothesis that TUDCA administered to rats prior to a myocardial infarction (MI) would exhibit anti-apoptotic effects and improve cardiac function. Prior to ligation of the left anterior descending (LAD) coronary artery, TUDCA (50 mg/ml, 400 mg/kg, IV) or PBS was administered to rats. Animals were sacrificed 24 hours after ligation for terminal transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and caspase-3 activity to assess apoptosis. Additional TUDCA or PBS treated rats underwent pre-operative,1 and 4 week transthoracic ultrasounds to assess heart function by quantification of shortening fraction (SF) and infarct area. TUNEL labeling of the cardiac tissue revealed a significant reduction in apoptotic cells in rats given TUDCA prior to ischemic injury (p = 0.05). In support of reducing apoptosis, caspase-3 activity in the TUDCA treated animals also decreased (p = 0.02). By 4 weeks, a significantly smaller infarct area was present in the TUDCA group compared to the PBS group (0.05 vs. 0.13 cm(2), p = NS) and there was also an improvement in SF. The results provide evidence for TUDCA as a viable treatment for reducing apoptosis in a model of myocardial infarction. Additional studies will distinguish the functional result of improved cell survival following infarction, suggesting the potential for clinical application of this anti-apoptotic drug in treatment of acute MI. [ABSTRACT FROM AUTHOR]
Copyright of American Journal of Chinese Medicine is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following myocardial infarction in rat.
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  Data: <searchLink fieldCode="AR" term="%22Rivard+AL%22">Rivard AL</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Steer+CJ%22">Steer CJ</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kren+BT%22">Kren BT</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rodrigues+CMP%22">Rodrigues CMP</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Castro+RE%22">Castro RE</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bianco+RW%22">Bianco RW</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Low+WC%22">Low WC</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22American+Journal+of+Chinese+Medicine%22">American Journal of Chinese Medicine</searchLink>. 2007, Vol. 35 Issue 2, p279-295. 17p.
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Black bear bile has been used in traditional Chinese medicine to treat liver and eye related illnesses for centuries. A major constituent of bile is ursodeoxycholic acid (UDCA). Recent analysis of the cellular effects of UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) have demonstrated their antiapoptotic properties through regulation of Bcl-2 family and survival signaling proteins (Bax, Bad, phosphatidylinositol-3-kinase). In this study, we tested the hypothesis that TUDCA administered to rats prior to a myocardial infarction (MI) would exhibit anti-apoptotic effects and improve cardiac function. Prior to ligation of the left anterior descending (LAD) coronary artery, TUDCA (50 mg/ml, 400 mg/kg, IV) or PBS was administered to rats. Animals were sacrificed 24 hours after ligation for terminal transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and caspase-3 activity to assess apoptosis. Additional TUDCA or PBS treated rats underwent pre-operative,1 and 4 week transthoracic ultrasounds to assess heart function by quantification of shortening fraction (SF) and infarct area. TUNEL labeling of the cardiac tissue revealed a significant reduction in apoptotic cells in rats given TUDCA prior to ischemic injury (p = 0.05). In support of reducing apoptosis, caspase-3 activity in the TUDCA treated animals also decreased (p = 0.02). By 4 weeks, a significantly smaller infarct area was present in the TUDCA group compared to the PBS group (0.05 vs. 0.13 cm(2), p = NS) and there was also an improvement in SF. The results provide evidence for TUDCA as a viable treatment for reducing apoptosis in a model of myocardial infarction. Additional studies will distinguish the functional result of improved cell survival following infarction, suggesting the potential for clinical application of this anti-apoptotic drug in treatment of acute MI. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of American Journal of Chinese Medicine is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1142/s0192415x07004813
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      – Code: eng
        Text: English
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              Text: 2007
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              Y: 2007
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