Article

Digestive Diseases and Sciences

, Volume 49, Issue 1, pp 65-72

First online:

Intestinal Barrier Function and Secretion in Methotrexate-Induced Rat Intestinal Mucositis

  • B. A. Carneiro-FilhoAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará
  • , I. P. F. LimaAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará
  • , D. H. AraujoAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará
  • , M. C. CavalcanteAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of CearáClinical Research Unit & Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará
  • , G. H. P. CarvalhoAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of CearáClinical Research Unit & Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará
  • , G. A. C. BritoAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará
  • , V. LimaAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará
  • , S. M. N. MonteiroAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of CearáClinical Research Unit & Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará
  • , F. N. SantosAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of CearáClinical Research Unit & Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará
    • , R. A. RibeiroAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará
    • , A. A. M. LimaAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Federal University of CearáClinical Research Unit & Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará

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Abstract

Chemotherapy-induced mucositis is an important dose-limiting and costly side effect for which there is no definitive prophylaxis or treatment. This is due in part to the lack of understanding of its pathophysiology and impact on intestinal function. The objectives of this study were to investigate the small intestine barrier function and electrolyte and water transport in an experimental model of methotrexate-induced mucositis, and to correlate these alterations with histological damage. Wistar rats were treated with methotrexate (1.5–3.5 mg/kg) for 3 days to induce mucositis. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following administration by gavage. Intestinal perfusion was performed in vivo for evaluation of water and electrolyte transports. Methotrexate-treated rats lost a significant amount of weight and presented a marked reduction in food intake. Methotrexate induced significant and dose-dependent villous atrophy and elongation of crypts in duodenum, jejunum, and ileum. Methotrexate also induced an increase in sodium and potassium secretion and an important reduction of the mucosa absorptive surface area, shown by the decrease in the mannitol excretion ratio. In conclusion, methotrexate caused major changes in small bowel function by disrupting intestinal permeability and inducing electrolyte secretion in parallel with substantial histological damage.

chemotherapy mucositis methotrexate intestinal permeability secretion