Changes in absorptive function of rat intestine injured by methotrexate

Kazumasa Naruhashi, Masayuki Nadai, Makoto Nakao, Nagao Suzuki, Toshitaka Nabeshima, Takaaki Hasegawa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

1. Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine. The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-β-lactam antibiotic cephalexin (CEX). Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg). 2. Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease. Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days. 3. Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day. Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity. 4. These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX. In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.

Original languageEnglish
Pages (from-to)980-986
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume27
Issue number12
DOIs
Publication statusPublished - 12-12-2000
Externally publishedYes

Fingerprint

Cephalexin
Methotrexate
Intestines
Small Intestine
Area Under Curve
Amine Oxidase (Copper-Containing)
Weights and Measures
Alkaline Phosphatase
Lactams
Active Biological Transport
Intestinal Mucosa
Oral Administration
Anti-Bacterial Agents
Wounds and Injuries
Therapeutics
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Naruhashi, Kazumasa ; Nadai, Masayuki ; Nakao, Makoto ; Suzuki, Nagao ; Nabeshima, Toshitaka ; Hasegawa, Takaaki. / Changes in absorptive function of rat intestine injured by methotrexate. In: Clinical and Experimental Pharmacology and Physiology. 2000 ; Vol. 27, No. 12. pp. 980-986.
@article{a7feaf0f88f4477e985c890f7ba36c40,
title = "Changes in absorptive function of rat intestine injured by methotrexate",
abstract = "1. Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine. The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-β-lactam antibiotic cephalexin (CEX). Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg). 2. Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease. Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days. 3. Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day. Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity. 4. These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX. In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.",
author = "Kazumasa Naruhashi and Masayuki Nadai and Makoto Nakao and Nagao Suzuki and Toshitaka Nabeshima and Takaaki Hasegawa",
year = "2000",
month = "12",
day = "12",
doi = "10.1046/j.1440-1681.2000.03380.x",
language = "English",
volume = "27",
pages = "980--986",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "12",

}

Changes in absorptive function of rat intestine injured by methotrexate. / Naruhashi, Kazumasa; Nadai, Masayuki; Nakao, Makoto; Suzuki, Nagao; Nabeshima, Toshitaka; Hasegawa, Takaaki.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 27, No. 12, 12.12.2000, p. 980-986.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Changes in absorptive function of rat intestine injured by methotrexate

AU - Naruhashi, Kazumasa

AU - Nadai, Masayuki

AU - Nakao, Makoto

AU - Suzuki, Nagao

AU - Nabeshima, Toshitaka

AU - Hasegawa, Takaaki

PY - 2000/12/12

Y1 - 2000/12/12

N2 - 1. Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine. The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-β-lactam antibiotic cephalexin (CEX). Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg). 2. Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease. Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days. 3. Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day. Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity. 4. These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX. In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.

AB - 1. Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine. The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-β-lactam antibiotic cephalexin (CEX). Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg). 2. Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease. Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days. 3. Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day. Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity. 4. These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX. In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.

UR - http://www.scopus.com/inward/record.url?scp=0033653195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033653195&partnerID=8YFLogxK

U2 - 10.1046/j.1440-1681.2000.03380.x

DO - 10.1046/j.1440-1681.2000.03380.x

M3 - Article

VL - 27

SP - 980

EP - 986

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 12

ER -