ArticlePharmaceutical research2009
Involvement of multidrug resistance-associated protein 1 in intestinal toxicity of methotrexate.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 21 citations in OpenAlex.
- How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Advances in Pharmacokinetic Mechanisms of Transporter-Mediated Herb-Drug Interactions.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice.Brain and behavior · 2016Article
- Increased susceptibility to methotrexate-induced toxicity in nonalcoholic steatohepatitis.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- A 30-years review on pharmacokinetics of antibiotics: is the right time for pharmacogenetics?Current drug metabolism · 2014Review
- Chalcogenopyrylium dyes as differential modulators of organic anion transport by multidrug resistance protein 1 (MRP1), MRP2, and MRP4.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Developmental pharmacogenetics in pediatric rheumatology: utilizing a new paradigm to effectively treat patients with juvenile idiopathic arthritis with methotrexate.Human genomics and proteomics : HGP · 2010Article
- Xenobiotic, bile acid, and cholesterol transporters: function and regulation.Pharmacological reviews · 2010Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMethotrexate (MTX) causes dose-limiting gastrointestinal toxicity due to exposure of intestinal tissues, and is a substrate of the multidrug resistance-associated protein (MRP) 1. Here we examine the involvement of MRP1, which is reported to be highly expressed in the proliferative crypt compartment of the small intestine, in the gastrointestinal toxicity of MTX.
methodsMTX was intraperitoneally administered to mrp1 gene knockout (mrp1 ((-/-))) and wild-type (mrp1 ((+/+))) mice. Body weight, food and water intake were monitored, intestinal histological studies and pharmacokinetics of MTX were examined.
resultsmrp1 ((-/-)) mice more severely decreased body weight, food and water intake than mrp1 ((+/+)) mice. Almost complete loss of villi throughout the small intestine in mrp1 ((-/-)) mice was observed, whereas the damage was only partial in mrp1 ((+/+)) mice. Plasma concentration and biliary excretion profiles of MTX were similar in mrp1 ((-/-)) and mrp1 ((+/+)) mice, though accumulation of MTX in immature proliferative cells isolated from mrp1 ((-/-)) mice was much higher compared to mrp1 ((+/+)) mice. Immunostaining revealed localization of Mrp1 in plasma membrane of the intestinal crypt compartment in mrp1 ((+/+)) mice, but not in mrp1 ((-/-)) mice.
conclusionMrp1 determines the exposure of proliferative cells in the small intestine to MTX, followed by gastrointestinal toxicity.
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