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

This work aimed to evaluate the activity of a lipid transfer protein isolated from Morinda citrifolia L. seeds, Mc LTP 1 , on the development of intestinal mucositis following irinotecan administration. Mc LTP 1 (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), glutathione (GSH), malondialdehyde (MDA), 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, Mc LTP 1 administration decreased mortality and diarrhea. Mc LTP 1 (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, Mc LTP 1 decreased the MPO, IL-1β, IL-6, and KC levels significantly by 74.7%, 42%, 92.9%, and 95.9%, respectively. Also, the expression of COX-2, NF-κB, and iNOS was reduced. Pretreatment with Mc LTP 1 (8mg/kg; i.v.) significantly reduced the MDA level and increased the duodenum homogenates' GSH level. Our study provides a potential new therapeutic for preventing irinotecan-induced mucositis, improved clinical parameters, reduced inflammation, and oxidative damage.