Sung Kyun Yim1,2, Kyoung Min Kim2,3, Chang-Hoon Lee1,2, Eun-Kee Song1,2, Seung Ok Lee1,2, Sang Wook Kim1,2, In Hee Kim1,2, Seong-Hun Kim1,2, Seung Young Seo1,2, Soo Teik Lee4,2. 1. Department of Internal Medicine, Jeonbuk National University Medical School and Hospital, Jeollabukdo, Republic of Korea. 2. Research Institute of Clinical Medicine, Jeonbuk National University, Jeollabukdo, Republic of Korea. 3. Department of Pathology, Jeonbuk National University Medical School and Hospital, Jeollabukdo, Republic of Korea. 4. Department of Internal Medicine, Jeonbuk National University Medical School and Hospital, Jeollabukdo, Republic of Korea; soo@jbnu.ac.kr.
Abstract
BACKGROUND/AIM: Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. MATERIALS AND METHODS: BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. RESULTS: M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. CONCLUSION: M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea. Copyright
BACKGROUND/AIM: Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. MATERIALS AND METHODS: BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. RESULTS:M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. CONCLUSION:M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea. Copyright
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