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Therapeutic effects of a lipid transfer protein isolated from Morinda citrifolia L. (noni) seeds on irinotecan-induced intestinal mucositis in mice

Abstract

This work aimed to evaluate the activity of a lipid transfer protein isolated from Morinda citrifolia L. seeds, McLTP1, on the development of intestinal mucositis following irinotecan administration. McLTP1 (0.5, 2, and 8 mg/kg, i.v.) was injected into mice 1h before irinotecan administration (75 mg/kg, i.p.; 4 days), and then for additional 6 days. Seven days after the first dose of irinotecan, diarrhea was assessed, and the intestine was removed for histological evaluation, assessment of intestinal over-contractility, measurement of myeloperoxidase (MPO), proinflammatory cytokines and chemokine (IL-1, IL-6, and KC levels - a murine homolog of human IL-8 chemokine), analysis of cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), and nitric oxide synthase (iNOS) expression. At the two highest doses, McLTP1 administration decreased mortality and diarrhea. McLTP1 (8 mg/kg, i.v.) significantly prevented irinotecan-induced intestinal damage and led to a reduction in over-contractility of the intestinal muscle (p < 0.05). Moreover, McLTP1 decreased the MPO, IL-1β, IL-6, and KC levels by 74.7%, 42%, 92.9%, and 95.9%, respectively. Also, the expression of COX-2, NF-κB, and iNOS was reduced. Our study provides a potential new therapeutic for preventing irinotecan-induced mucositis, improved clinical parameters, and reduced inflammation.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgments

This work was supported by research grants from Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Award Number: PR2-0101-00054.01.00/15 PRONEX/FUNCAP/CNPq — Edital 02/2015), and scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Funding

This research project was supported by the Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Award Number: PR2-0101-00054.01.00/15 PRONEX/FUNCAP/CNPq - Edital 02/2015).

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Authors

Contributions

NMNA and HDO had the idea for the article and provided the study materials, reagents, laboratory samples, animals, and instrumentation. ASC and DCOC purified the protein used in the experiments (McLTP1). LDC, GFPR, LMAR, TFGS, RCLJr, DVTW, RFCL, AAVS, and PJCM collected the data, performed the literature search and data analysis, and drafted and critically revised the published work. All authors read and approved the manuscript, all data were generated in-house, and no paper mill was used.

Corresponding author

Correspondence to Hermógenes David de Oliveira.

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The authors declare no competing interests.

Ethical approval

This study was approved by the “Animal Use Ethics Committee (CEUA)” of the Federal University of Ceará vide protocol no. 93/15. The guidelines of the “National Council for the Control of Animal Experimentation (CONCEA)” were followed for all animal experiments and care of animals.

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All authors have agreed to publish this study.

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The authors declare no competing interests.

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do Carmo, L.D., de Fátima Pinheiro Rangel, G., Rabelo, L.M.A. et al. Therapeutic effects of a lipid transfer protein isolated from Morinda citrifolia L. (noni) seeds on irinotecan-induced intestinal mucositis in mice. Naunyn-Schmiedeberg's Arch Pharmacol (2022). https://doi.org/10.1007/s00210-022-02267-7

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  • DOI: https://doi.org/10.1007/s00210-022-02267-7

Keywords

  • Morinda citrifolia
  • Protein therapeutics
  • Lipid transfer protein
  • Chemotherapy
  • Intestinal mucositis