Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model.
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.
Huang
Tien-Yu
TY
Graduate Institute of Medical Sciences, National Defense Medical Center, 161 Sec. 6 Min-Chuan E. Road, Neihu, Taipei, Taiwan.
Chu
Heng-Cheng
HC
Lin
Yi-Ling
YL
Ho
Whae-Hong
WH
Hou
Hsien-San
HS
Chao
You-Chen
YC
Liao
Ching-Len
CL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000627:therapeutic use*; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D023041:Xenograft Model Antitumor Assays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D008911:Minocycline; D005472:Fluorouracil