Abstract
Neurotoxicity and nephrotoxicity are the major dose-limiting factors for the clinical use of colistin against multidrug-resistant (MDR) Gram-negative bacteria. This study aimed to investigate the neurotoxic and nephrotoxic effects of colistin formulated with in-house synthesized sodium deoxycholate sulfate (SDCS) in a mouse model. Male mice C57BL/6 were randomly divided into four groups: control (saline solution), colistin (15 mg/kg/day), colistin:SDCS 1:1, and colistin:SDCS 1:2. In the colistin:SDCS treatment groups, the dosage was 15 mg/kg/day colistin equivalent; all mice were treated for 7 successive days. The thermal tolerance, body weight gain and organ weights were measured. The levels of serum blood urea nitrogen (BUN), creatinine (Cr), superoxide dismutase (SOD), and catalase (CAT) were assessed. Histopathological damages were assessed on mice organ. The colistin:SDCS formulations significantly improved thermal pain response of the mice comparable to the control group. The administration did not impair kidney function as evidence from BUN and Cr results; however, the oxidative stress biomarkers decreased in the colistin and colistin-SDCS treated mice. Several abnormalities were observed in the kidney, liver, spleen, and sciatic nerve tissues following colistin treatment, which indicated evidence of toxicity. The colistin-SDCS formulations were associated with less acute toxicity and fewer nephrotoxic and neurotoxic changes compared with the colistin alone group which indicated that SDCS attenuated colistin nephrotoxicity and neurotoxicity. This study highlights the potential application of colistin formulated with SDCS for safer clinical use against MDR Gram-negative bacteria.
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Acknowledgements
The authors would like to thank Sunisa Kaewpaiboon and Titpawan Nakpheng for assisting in experimental works.
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This work was supported by National Science, Research and Innovation Fund and Prince of Songkla University (PHA6601221S).
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MAKMB, JN, and TS contributed to the study conception and design. Material preparation, data collection and analysis were performed by MAKMB, and JN. The first draft of the manuscript was written by MAKMB, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Bintang, M.A.K.M., Nopparat, J. & Srichana, T. In vivo evaluation of nephrotoxicity and neurotoxicity of colistin formulated with sodium deoxycholate sulfate in a mice model. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3243–3252 (2023). https://doi.org/10.1007/s00210-023-02531-4
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DOI: https://doi.org/10.1007/s00210-023-02531-4