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St. Johns wort attenuates irinotecan-induced diarhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis
journal contribution
posted on 2006-10-15, 00:00 authored by Z P Hu, X X Yang, S Chan, A L Xu, Wei DuanWei Duan, Y Z Zhu, F S Sheu, U Boelsterli, E Chan, Q Zhang, J C Wang, P Rachel Ee, H Koh, M Huang, S F ZhouDiarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5–11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5–11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.
History
Journal
Toxicology and applied pharmacologyVolume
216Issue
2Pagination
225 - 237Publisher
Academic PressLocation
San Diego Calif.Publisher DOI
ISSN
0041-008XeISSN
1096-0333Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2006, Elsevier Inc.Usage metrics
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