Mechanisms underlying methotrexate-induced pulmonary toxicity

Title
Mechanisms underlying methotrexate-induced pulmonary toxicity
Authors
김연정송미류재천
Keywords
methotrexate; pulmonary toxicity; mechanism; p38 MAPK
Issue Date
2009-07
Publisher
Expert Opinion on Drug Safety
Citation
VOL 8, NO 4, 451-458
Abstract
Methotrexate (MTX) has been widely used for the treatment of inflammatory diseases and rheumatoid arthritis, as well as a variety of tumors. However, MTX-induced pulmonary toxicity is a serious and unpredictable side effect of the therapy, which includes allergic, cytotoxic or immunologic reactions, and is a major clinical problem. Objective: To summarize the mechanisms of action involved in MTX-induced pulmonary toxicity. Methods: We reviewed the literature describing MTX-induced adverse pulmonary effects and the mechanisms of action underlying MTX-induced pulmonary toxicity. Conclusion: The mechanisms underlying MTX toxicity are complex. The clinical effects may be attributable to both the anti-inflammatory and immunosuppressive effects of MTX. The mechanisms causing the side effects of MTX include mutation of the genotype, inhibition of transport, MTX-polyglutamates and P-glycoprotein binding with MTX. The p38 MAPK-signaling pathway is especially associated with a pulmonary inflammatory response. These mechanisms can be applied to optimize drug treatment.
URI
http://pubs.kist.re.kr/handle/201004/35821
ISSN
1474-0338
Appears in Collections:
KIST Publication > Article
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