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Biochem Biophys Res Commun. 2009 Nov 27;389(4):634-9. doi: 10.1016/j.bbrc.2009.09.041. Epub 2009 Sep 16.

Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model.

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Graduate Institute of Medical Sciences, National Defense Medical Center, 161 Sec. 6 Min-Chuan E. Road, Neihu, Taipei, Taiwan.


Minocycline exerts anti-inflammatory and anti-apoptotic effects distinct from its antimicrobial function. In this study we investigated the effect of this drug on chemotherapy-induced gut damage. Body weight loss results, diarrhea scores, and villi measurements showed that minocycline attenuated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU). Minocycline repressed the expression of TNF-alpha, IL-1beta, and iNOS, decreased the apoptotic index, and inhibited poly(ADP-ribose) polymerase-1 (PARP-1) activity in the mouse small intestine. In vitro experiments showed that minocycline suppressed the upregulation of PARP-1 activity in enterocyte IEC-6 cells treated with 5-FU. In addition, minocycline treatment appeared to enhance the antitumor effects of 5-FU in tumor CT-26 xenograft mice. Our results indicate that minocycline protects mice from gut injury induced by 5-FU and enhances the antitumor effects of 5-FU in xenograft mice. These observations suggest that minocycline treatment may benefit patients undergoing standard cancer chemotherapy by alleviating chemical-associated intestinal mucositis.

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