|
|||||
|
|
Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model |
|
| Authors: | Tien-Yu Huang Heng-Cheng Chu Whae-Hong Ho You-Chen Chao |
| Affiliation: | a Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan b Division of Gastroenterology, Tri-Service General Hospital, Taipei, Taiwan c Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan d Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan e Division of Gastroenterology, Taipei Tzu Chi General Hospital, Taipei, Taiwan |
| Abstract: | 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-α, IL-1β, 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. |
| Keywords: | Minocycline Mucositis 5-Fluorouracil Chemotherapy |
| 本文献已被 ScienceDirect 等数据库收录！ | |