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The antirheumatic drug sulfasalazine ameliorates acute renal failure (ARF) induced by polymyxin B

The Journal of Antibiotics volume 78, pages 511–515 (2025)Cite this article

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Abstract

Polymyxin B (PMB) is a polypeptide antibiotic active against multidrug-resistant bacteria, including multidrug-resistant Pseudomonas aeruginosa (MDRP). However, PMB frequently initiates serious acute renal failure (ARF). Our recent study demonstrated that PMB-induced ARF is triggered by inflammatory responses mediated by activation of the NOD-like receptors protein 3 (NLRP3) inflammasome. Here, we provide evidence that sulfasalazine (SSZ), a clinically-used disease-modifying antirheumatic drug (DMARD), can ameliorate PMB-induced ARF in a mouse model of ARF. Since SSZ strongly inhibited the NLRP3 inflammasome activation induced by PMB in macrophages, as previously demonstrated, the amelioration of PMB-induced ARF appears to be brought about by the inhibition of the NLRP3 inflammasome activation. Thus, if SSZ could be effectively utilized in clinical practice, it may be possible to overcome ARF caused by polypeptide antibiotics.

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Acknowledgements

We thank all members of Lab of Health Chemistry for helpful discussions. This work was supported by JSPS KAKENHI Grant Numbers JP21H02691, JP21H02620, JP22J20257, JP24K02237, JP24K22011 and JP24K02173. This work was also supported by the Division for Interdisciplinary Advanced Research and Education (DIARE) Tohoku University.

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Author notes

  1. These authors contributed equally: Kohei Otani, Tomohiro Kagi, Takuya Noguchi

Authors and Affiliations

  1. Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

    Kohei Otani, Tomohiro Kagi, Takuya Noguchi, Sara Suzuki, Yusuke Hirata & Atsushi Matsuzawa

  2. Department of Medical Biochemistry, School of Pharmacy, Iwate Medical University, Yahaba, Japan

    Takuya Noguchi

Authors
  1. Kohei Otani
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  2. Tomohiro Kagi
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  3. Takuya Noguchi
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  4. Sara Suzuki
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  5. Yusuke Hirata
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  6. Atsushi Matsuzawa
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Correspondence to Takuya Noguchi or Atsushi Matsuzawa.

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Otani, K., Kagi, T., Noguchi, T. et al. The antirheumatic drug sulfasalazine ameliorates acute renal failure (ARF) induced by polymyxin B. J Antibiot 78, 511–515 (2025). https://doi.org/10.1038/s41429-025-00835-6

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  • DOI: https://doi.org/10.1038/s41429-025-00835-6

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