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Lipid Emulsion Inhibits Apoptosis Induced by a Toxic Dose of Verapamil via the Delta-Opioid Receptor in H9c2 Rat Cardiomyoblasts

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Abstract

The goals of this study were to investigate the effects of lipid emulsion (LE) on apoptosis induced by a toxic dose of verapamil in H9c2 cells and to elucidate the associated cellular mechanism. The effects of LE alone and combined with an inhibitor on the decreases in cell counts and viability induced by verapamil and diltiazem were examined using the MTT assay. The effects of verapamil alone, combined LE and verapamil treatment, and combined inhibitor, LE and verapamil treatment on cleaved caspase-3, caspase-8 and Bax expression, were examined using Western blotting. The effects of verapamil alone and combined with LE on the number of TUNEL-positive H9c2 cells were also examined. LE attenuated the decreases in cell counts and viability induced by verapamil and diltiazem. However, the magnitude of the LE-mediated attenuation of decreased cell viability was enhanced by verapamil compared with diltiazem treatment. Naloxone, naltrindole hydrochloride, LY294002 and MK-2206 inhibited the LE-mediated attenuation of increased cleaved caspase-3 and caspase-8 expression induced by verapamil. LE attenuated the increase in the number of TUNEL-positive cell induced by verapamil. These results suggest that LE attenuates apoptosis induced by verapamil via activation of the delta-opioid receptor, phosphoinositide 3-kinase and Akt.

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Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A01054105).

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju-si, 52727, Republic of Korea

    Seong-Ho Ok, Mun Hwan Choi, Il-Woo Shin & Ju-Tae Sohn

  2. Department of Anesthesiology, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea

    Soo Hee Lee, Sebin Kang & Jiah Oh

  3. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea

    Jeong Yeol Han

  4. Institutes of Health Sciences, Gyeongsang National University, Jinju-si, Republic of Korea

    Ju-Tae Sohn

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Correspondence to Ju-Tae Sohn.

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Seong-Ho Ok is currently receiving a Grant from National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A01054105). The remaining authors have declared that no competing interest exists.

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Ok, SH., Choi, M.H., Shin, IW. et al. Lipid Emulsion Inhibits Apoptosis Induced by a Toxic Dose of Verapamil via the Delta-Opioid Receptor in H9c2 Rat Cardiomyoblasts. Cardiovasc Toxicol 17, 344–354 (2017). https://doi.org/10.1007/s12012-016-9392-9

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