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Skeletal muscle post-conditioning by diazoxide, anti-oxidative and anti-apoptotic mechanisms

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Abstract

Pretreatment with diazoxide, KATP channel opener, increases tissue tolerance against ischemia reperfusion (IR) injury. In clinical settings pretreatment is rarely an option therefore we evaluated the effect of post-ischemic treatment with diazoxide on skeletal muscle IR injury. Rats were treated with either saline, diazoxide (KATP opener; 40 mg/kg) or 5-hydroxydecanoate (5-HD; mitochondrial KATP inhibitor; 40 mg/kg) after skeletal muscle ischemia (3 h) and reperfusion (6, 24 or 48 h). Tissue contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl-2 protein expression and muscle histology were determined. Apoptosis was examined (24 and 48 h) after ischemia. IR induced severe histological damage, increased MDA content and Bax expression (24 and 48 h; p < 0.01) and decreased CAT and SOD activities (6 and 24 h, p < 0.01 and 48 h, p < 0.05), with no significant effect on Bcl-2 expression. Diazoxide reversed IR effects on MDA (6 and 24 h; p < 0.05), SOD (6 and 24 h; p < 0.01) and CAT (6 and 48 h, p < 0.05 and 24 h p < 0.01) and tissue damage. Diazoxide also decreased Bax (24 and 48 h; p < 0.05) and increased Bcl-2 protein expression (24 and 48 h; p < 0.01). Post-ischemic treatment with 5-HD had no significant effect on IR injury. Number of apoptotic nuclei in IR and 5-HD treated groups significantly increased (p < 0.001) while diazoxide decreased apoptosis (p < 0.01). The results suggested that post-ischemic treatment with diazoxide decrease oxidative stress in acute phase which modulates expression of apoptotic proteins in the late phase of reperfusion injury. Involvement of KATP channels in this effect require further evaluations.

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Acknowledgments

All authors appreciate Physiology Research Center, Tehran University of Medical Sciences, for supporting experimental tools and devices.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Moghtadaei

  2. Physiology Research Center, Tehran University of Medical Sciences, P.O. Box 14515-763, Tehran, Iran

    Rouhollah Habibey, Marjan Ajami & Hamidreza Pazoki-Toroudi

  3. Department of Nutrition, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Marjan Ajami

  4. Cellular and Molecular Research Center (CMRC), Tehran University of Medical Sciences, Tehran, Iran

    Mansoureh Soleimani

  5. Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran

    Soltan Ahmed Ebrahimi

  6. Nano Vichar Pharmaceutical Ltd, Tehran, Iran

    Hamidreza Pazoki-Toroudi

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  1. Mehdi Moghtadaei
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Correspondence to Hamidreza Pazoki-Toroudi.

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Moghtadaei, M., Habibey, R., Ajami, M. et al. Skeletal muscle post-conditioning by diazoxide, anti-oxidative and anti-apoptotic mechanisms. Mol Biol Rep 39, 11093–11103 (2012). https://doi.org/10.1007/s11033-012-2015-z

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