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

do Carmo, Luana David; de Fátima Pinheiro Rangel, Gisele; Rabelo, Liviane Maria Alves; de  Fátima Goebel de Souza, Tamiris; Júnior, Roberto César Pereira Lima; Wong, Deysi Viviana Tenazoa; de Carvalho Leitão, Renata Ferreira; da Silva, Alfredo Augusto Vasconcelos; Magalhães, Pedro Jorge Caldas; Costa, Andréa Santos; de Carvalho Oliveira Campos, Dyély; de Alencar, Nylane Maria Nunes; de Oliveira, Hermógenes David

doi:10.1007/s00210-022-02267-7

Original Article
Published: 01 July 2022

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

Luana David do Carmo¹,
Gisele de Fátima Pinheiro Rangel¹,
Liviane Maria Alves Rabelo¹,
Tamiris de Fátima Goebel de Souza¹,
Roberto César Pereira Lima Júnior¹,
Deysi Viviana Tenazoa Wong¹,
Renata Ferreira de Carvalho Leitão¹,
Alfredo Augusto Vasconcelos da Silva¹,
Pedro Jorge Caldas Magalhães¹,
Andréa Santos Costa²,
Dyély de Carvalho Oliveira Campos²,
Nylane Maria Nunes de Alencar¹ &
Hermógenes David de Oliveira²

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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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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 and Affiliations

Department of Physiology and Pharmacology, Federal University of Ceará, Campus do Porangabuçu, Fortaleza, Ceará, 60430-275, Brazil
Luana David do Carmo, Gisele de Fátima Pinheiro Rangel, Liviane Maria Alves Rabelo, Tamiris de Fátima Goebel de Souza, Roberto César Pereira Lima Júnior, Deysi Viviana Tenazoa Wong, Renata Ferreira de Carvalho Leitão, Alfredo Augusto Vasconcelos da Silva, Pedro Jorge Caldas Magalhães & Nylane Maria Nunes de Alencar
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Campus do Pici Prof. Prisco Bezerra, Fortaleza, Ceará, 60440-900, Brazil
Andréa Santos Costa, Dyély de Carvalho Oliveira Campos & Hermógenes David de Oliveira

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Luana David do Carmo
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Gisele de Fátima Pinheiro Rangel
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Liviane Maria Alves Rabelo
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Tamiris de Fátima Goebel de Souza
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Roberto César Pereira Lima Júnior
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Deysi Viviana Tenazoa Wong
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Renata Ferreira de Carvalho Leitão
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Alfredo Augusto Vasconcelos da Silva
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Pedro Jorge Caldas Magalhães
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Andréa Santos Costa
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Dyély de Carvalho Oliveira Campos
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Nylane Maria Nunes de Alencar
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Hermógenes David de Oliveira
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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.

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Correspondence to Hermógenes David de Oliveira.

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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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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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Received: 21 March 2022
Accepted: 21 June 2022
Published: 01 July 2022
DOI: https://doi.org/10.1007/s00210-022-02267-7

Keywords

Morinda citrifolia
Protein therapeutics
Lipid transfer protein
Chemotherapy
Intestinal mucositis