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Protective effects of antioxidative serotonin derivatives isolated from safflower against postischemic myocardial dysfunction

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Abstract

N-(p-Coumaroyl)serotonin (C) and N-feruroylserotonin (F) with antioxidative activity are present in safflower oil. The protective effects of C and F were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Changes in cellular levels of high phosphorous energy, NO and Ca2+ in the heart together with simultaneous recordings of left ventricular developed pressure (LVDP) were monitored by an nitric oxide (NO) electrode, fluorometry and 31P-NMR. The rate of recovery of LVDP from ischemia by reperfusion was 30.8% in the control, while in the presence of C or F a gradual increase to 63.2 or 61.0% was observed. Changes of transient NO signals (TNO) released from heart tissue in one contraction (LVDP) were observed to be upside-down with respect to transient fura-2-Ca2+ signals (TCa) and transient O2 signals detected with a pO2 electrode. At the final stage of ischemia, the intracellular concentration of Ca2+ ([Ca2+]i) and the release of NO increased with no twitching and remained at a high steady level. The addition of C increased the NO level at the end of ischemia compared with the control, but [Ca2+]i during ischemia decreased. On reperfusion, the increased diastolic level of TCa and TNO returned rapidly to the control level with the recovery of LVDP. By in vitro EPR, C and F were found to directly quench the activity of active radicals. Therefore, it is concluded that the antioxidant effects of two derivatives isolated from safflower play an important role in ischemia-reperfusion hearts in close relation with NO.

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Authors and Affiliations

  1. Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan

    Yoshihiro Hotta, Tatsuya Muto, Xiuli Lu, Michio Yajima, Naohisa Ishikawa & Kunihiro Miyazeki

  2. Faculty of Pharmaceutical Science, Nagoya City University, Nagoya, 467-8603, Japan

    Akito Nagatsu, Hajime Mizukami & Jinsaku Sakakibara

  3. Cell Biology and Metabolism Branch, NICHD, NIH, Bethesda, MD, 20892-5430, USA

    Wei Liu

  4. Department of Cardiovascular Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan

    Chihiro Narumiya

  5. Department of Anatomy, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan

    Norio Kawai

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  1. Yoshihiro Hotta
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  2. Akito Nagatsu
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Hotta, Y., Nagatsu, A., Liu, W. et al. Protective effects of antioxidative serotonin derivatives isolated from safflower against postischemic myocardial dysfunction. Mol Cell Biochem 238, 151–162 (2002). https://doi.org/10.1023/A:1019992124986

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