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.

• Authors: 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, Andréa Santos Costa, Dyély de Carvalho Oliveira Campos, Nylane Maria Nunes de Alencar, Hermógenes David de Oliveira
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 395 Issue 9 Pg. 1097-1107 (09 2022) ISSN: 1432-1912 [Electronic] Germany
• PMID: 35776167 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Antineoplastic Agents
• Carrier Proteins
• Chemokines
• Interleukin-6
• NF-kappa B
• lipid transfer protein
• Irinotecan
• Cyclooxygenase 2

Topics

• Animals
• Antineoplastic Agents
• Carrier Proteins
• Chemokines
• Cyclooxygenase 2
• Diarrhea
• Humans
• Interleukin-6
• Intestines
• Irinotecan
• Mice
• Morinda
• Mucositis
• NF-kappa B
• Seeds