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Sparstolonin B Attenuates Hypoxia-Induced Apoptosis, Necrosis and Inflammation in Cultured Rat Left Ventricular Tissue Slices

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Abstract

Purpose

Ischemia/reperfusion results in tissue damage, a rapid increase in cytokines and chemokines and inflammatory cell infiltration. Herein we investigated the ability of a selective TLR2/4 antagonist, Sparstolonin B (SsnB), to protect rat cultured left ventricular tissue (LV) slices from hypoxic injury by inhibiting the myocardial inflammatory response independent of inflammatory cell infiltration.

Methods and Results

Media Lactate dehydrogenase (LDH) levels were measured to reflect hypoxia-induced cytotoxicity and cell injury with and without SsnB. Incubation with SsnB (15 and 30 μM) significantly reduced by 20 and 40 %, respectively, the amount of LDH released from the hypoxic LV slices. TUNEL staining showed that SsnB significantly attenuated the levels of hypoxia-induced apoptotic cells from 61.5 ± 4.0 to 27.0 ± 2.1 (15 μM SsnB) and 23.5 ± 2.2 (30 μM SsnB) cells/unit area. Similarly, the Periodic Acid-Schiff (PAS) staining of ischemic areas in untreated hypoxic LV slices was increased 17 fold from 0.26 ± 0.09 to 4.41 ± 0.43 %, while in hypoxic slices incubated with 15 and 30 μM of SsnB, the PAS positive ischemic areas were increased by only 6.4 fold to 1.66 ± 0.39 % and 3.8 fold to 1.00 ± 0.22 %, respectively. Rt-PCR confirmed that MCP1 and IL-6 expression during hypoxia was elevated by 2 and 4 fold, respectively, while their up-regulation was significantly inhibited (i.e., <0.7 fold increase) by SsnB.

Conclusion

The selective TLR2/4 antagonist, Sparstolonin B, can substantially protect LV myocardium via its ability to inhibit injury resulting from hypoxic myocardial-generated inflammation. Accordingly SsnB has potential as a therapeutic agent for the attenuation of myocardial ischemia-reperfusion injury.

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Acknowledgments

This work was supported by the National Heart, Lung and Blood Institute at the National Institutes of Health (R21-HL-089483 to J.S.J. and R21AT006767 and R01HL116626 to D.F.).

Disclosures

None declared.

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, 29208, USA

    Qing Liu, Jianping Li, Shaiban Jubair, Daping Fan & Joseph S. Janicki

  2. The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China

    Qing Liu, Dawei Wang & Yi Luo

Authors
  1. Qing Liu
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  2. Jianping Li
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  3. Shaiban Jubair
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  4. Dawei Wang
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  5. Yi Luo
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  6. Daping Fan
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  7. Joseph S. Janicki
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Correspondence to Joseph S. Janicki.

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Liu, Q., Li, J., Jubair, S. et al. Sparstolonin B Attenuates Hypoxia-Induced Apoptosis, Necrosis and Inflammation in Cultured Rat Left Ventricular Tissue Slices. Cardiovasc Drugs Ther 28, 433–439 (2014). https://doi.org/10.1007/s10557-014-6545-6

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  • DOI: https://doi.org/10.1007/s10557-014-6545-6

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