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Research Article

Cancer Research Frontiers. 2016 Feb; 2(1): 33-42. doi: 10.17980/2016.33

Influence of H2-receptor antagonists on intestinal mucositis induced by 5-fluorouracil in rats

 

Takafumi Ichikawa1*, Yoichi Saegusa2, Motoko Nakano3, Rei Kawashima1, Fumitaka Kawakami1, Tatsunori Maekawa1, Setsuko Sugawara1, Kazuhiko Ishihara1

1 Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan

2 Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan

3 Tokushima Research Center, Taiho Pharmaceutical Co. Ltd., Tokushima, Japan

 
*Corresponding author: Prof. Takafumi Ichikawa. Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan. Tel/Fax: +81 427 788863. E-mail: t.ichika@kitasato-u.ac.jp

Citation: Takafumi Ichikawa, et al. Influence of H2-receptor antagonists on intestinal mucositis induced by 5-fluorouracil in rats. Cancer Research Frontiers. 2016 Feb; 2(1): 33-42. doi: 10.17980/2016.33

Copyright: @ 2016 Takafumi Ichikawa, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing Interests: The authors declare that there are no competing interests.

Received Sept 29, 2015; Revised Dec 18, 2015; Accepted Dec 29, 2015. Published Jan 22, 2016

 

 

Abstract

AIM: Although histamine (H2) receptor antagonists appear clinically beneficial; their effects on chemotherapy-induced mucositis remain poorly understood. Therefore, we compared the influences of cimetidine, famotidine, and lafutidine on intestinal mucositis induced by 5-fluorouracil (5-FU) in rats. Simultaneously, we assessed whether the antitumor efficacy was influenced by these treatments for mucositis.

METHODS: Rats were divided into five groups. The first group (control) was orally administered 0.5% carboxymethylcellulose once daily for 5 or 7 days. The second, third, fourth, and fifth groups were treated with 5-FU (30 or 50 mg/kg), 5-FU plus cimetidine (100 mg/kg), 5-FU plus famotidine (5 mg/kg), and 5-FU plus lafutidine (30 mg/kg), respectively. We compared the levels of antitumor activity and mucosal damage among these groups. Furthermore, the possible participation of capsaicin-sensitive afferent neurons was investigated.

RESULTS: 5-FU was shown to reduce weight gain and intestinal mucin accumulation. Oral administration of the H2-receptor antagonists had no effect on the antitumor activity of 5-FU. Lafutidine, but neither cimetidine nor famotidine, prevented the 5-FU-induced side effects, including reduction of bodyweight gain, mucosal damage, and decrease in mucin content. These beneficial effects disappeared after capsaicin-sensitive afferent neurons were ablated.

CONCLUSION: Second-generation H2-receptor antagonists may lead to a more effective prevention of chemotherapy-induced intestinal mucositis.

Key Words: Cancer chemotherapy, capsaicin-sensitive afferent neurons, 5-fluorouracil, intestinal mucositis, H2-receptor antagonists, rat

 

 

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