Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats

被引:63
|
作者
Maeda, Tomoko [1 ]
Miyazono, Yuko [1 ]
Ito, Kousei [2 ]
Hamada, Kazuma [1 ]
Sekine, Shuichi [1 ]
Horie, Toshiharu [1 ]
机构
[1] Chiba Univ, Dept Biopharmaceut, Grad Sch Pharmaceut Sci, Chuo Ku, Chiba 2608675, Japan
[2] Univ Tokyo, Dept Pharm, Fac Med, Tokyo Univ Hosp,Bunkyo Ku, Tokyo 1138655, Japan
关键词
Methotrexate; Reactive oxygen species; Intestinal permeability; Chemiluminescence; N-Acetylcysteine; Glutathione; AGED GARLIC EXTRACT; PROSTAGLANDIN E-1; SYNTHETIC ANALOG; EPITHELIAL-CELLS; TIGHT JUNCTIONS; INDUCED DAMAGE; GROWTH-FACTOR; CHEMOTHERAPY; TOXICITY; CANCER;
D O I
10.1007/s00280-009-1119-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We previously demonstrated the increase of reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity in the small intestine of methotrexate (MTX)-treated rats. In the present study, we investigated the role of ROS modulating intestinal mucosal permeability in this damage. MTX (20 mg/kg body weight) was administered to rats intravenously. N-Acetylcysteine (NAC; 80 mg/kg body wt), an antioxidant and a precursor of glutathione (GSH) was administered to rats intraperitoneally to investigate the contribution of ROS to the intestinal permeability enhancement. Intestinal permeability was evaluated by determining that of a poorly absorbable marker, fluorescein isothiocyanate-labeled dextran (FD-4; average molecular mass, 4.4 kDa) using the in vitro everted intestine technique. The occurrence of oxidative stress in the small intestine was assayed by measuring chemiluminescence and thiobarbituric acid reactive substances (TBARS) productions in mucosal homogenates of the small intestine. The mucosal permeability of FD-4 significantly (p < 0.01) increased in MTX-treated rats compared with control rats, as demonstrated by a twofold increase of FD-4 permeation clearance. This suggests an increase in paracellular permeability. Interestingly, the ROS production was observed preceding the increase of paracellular permeability. Treatment with NAC prevented the MTX-induced ROS production and the increase of paracellular permeability. NAC protected the small intestine of rats from MTX-induced change in paracellular permeability, suggesting that ROS played an important role in the enhanced paracellular permeability.
引用
收藏
页码:1117 / 1123
页数:7
相关论文
共 50 条
  • [31] Effect of oxidative stress and ageing on small intestine and colon
    Almuhammadi, A.
    Grundy, D.
    NEUROGASTROENTEROLOGY AND MOTILITY, 2016, 28 : 27 - 27
  • [32] Protective effect of prostaglandins on the methotrexate induced damage of small intestine in rats
    Gao, F
    Horie, T
    IN VIVO, 2000, 14 (03): : 453 - 456
  • [33] Differential effect of oxidative stress on intestinal apparent permeability of drugs transported by paracellular and transcellular route
    Pankaj Dixit
    Dinesh Kumar Jain
    Jaypal Singh Rajpoot
    European Journal of Drug Metabolism and Pharmacokinetics, 2012, 37 : 203 - 209
  • [34] Differential effect of oxidative stress on intestinal apparent permeability of drugs transported by paracellular and transcellular route
    Dixit, Pankaj
    Jain, Dinesh Kumar
    Rajpoot, Jaypal Singh
    EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 2012, 37 (03) : 203 - 209
  • [35] Preclinical Efficacy of Melatonin to Reduce Methotrexate-Induced Oxidative Stress and Small Intestinal Damage in Rats
    Viswa Kalyan Kolli
    Premila Abraham
    Bina Isaac
    N. Kasthuri
    Digestive Diseases and Sciences, 2013, 58 : 959 - 969
  • [36] Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats
    Arslan, Aynur
    Ozcicek, Fatih
    Cimen, Ferda Keskin
    Altuner, Durdu
    Yarali, Oguzhan
    Kurt, Nezahat
    Tumkaya, Levent
    Ozturk, Cengiz
    Suleyman, Halis
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2015, 8 (07): : 10491 - 10500
  • [37] Preclinical Efficacy of Melatonin to Reduce Methotrexate-Induced Oxidative Stress and Small Intestinal Damage in Rats
    Kolli, Viswa Kalyan
    Abraham, Premila
    Isaac, Bina
    Kasthuri, N.
    DIGESTIVE DISEASES AND SCIENCES, 2013, 58 (04) : 959 - 969
  • [38] Localisation of drug permeability along the rat small intestine, using markers of the paracellular, transcellular and some transporter routes
    Lacombe, O
    Woodley, J
    Solleux, C
    Delbos, JM
    Boursier-Neyret, C
    Houin, G
    EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2004, 23 (4-5) : 385 - 391
  • [39] Oxidative stress evidence in rats treated with thyroxin
    Joanta, A
    Andrei, S
    Krausz, T
    Filip, A
    Suciu, S
    Clichici, S
    Dorofteiu, M
    BULLETIN OF THE UNIVERSITY OF AGRICULTURAL SCIENCES AND VETERINARY MEDICINE, VOLS 57 AND 58: VETERINARY MEDICINE, 2002, 57-8 : 610 - 618
  • [40] MICROVASCULAR PERMEABILITY IN ISOLATED VASCULARLY PERFUSED SMALL-INTESTINE OF RATS
    KRANEVELD, AD
    KOSTER, AS
    NIJKAMP, FP
    AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (06): : G1170 - G1178