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Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10

PURPOSE: Effective methods to ameliorate radiation enteropathy have not been developed. To address this issue, we investigated the reduced form of coenzyme Q10 (rCoQ10) as a potential radioprotector in a mouse model. METHODS AND MATERIALS: rCoQ10 was added to a standard laboratory mouse diet at a fi...

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Autores principales: Shimizu, Yasuyuki, Mukumoto, Naritoshi, Idrus, Nelly, Akasaka, Hiroaki, Inubushi, Sachiko, Yoshida, Kenji, Miyawaki, Daisuke, Ishihara, Takeaki, Okamoto, Yoshiaki, Yasuda, Takahiro, Nakahana, Makiko, Sasaki, Ryohei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460318/
https://www.ncbi.nlm.nih.gov/pubmed/31011668
http://dx.doi.org/10.1016/j.adro.2019.01.006
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author Shimizu, Yasuyuki
Mukumoto, Naritoshi
Idrus, Nelly
Akasaka, Hiroaki
Inubushi, Sachiko
Yoshida, Kenji
Miyawaki, Daisuke
Ishihara, Takeaki
Okamoto, Yoshiaki
Yasuda, Takahiro
Nakahana, Makiko
Sasaki, Ryohei
author_facet Shimizu, Yasuyuki
Mukumoto, Naritoshi
Idrus, Nelly
Akasaka, Hiroaki
Inubushi, Sachiko
Yoshida, Kenji
Miyawaki, Daisuke
Ishihara, Takeaki
Okamoto, Yoshiaki
Yasuda, Takahiro
Nakahana, Makiko
Sasaki, Ryohei
author_sort Shimizu, Yasuyuki
collection PubMed
description PURPOSE: Effective methods to ameliorate radiation enteropathy have not been developed. To address this issue, we investigated the reduced form of coenzyme Q10 (rCoQ10) as a potential radioprotector in a mouse model. METHODS AND MATERIALS: rCoQ10 was added to a standard laboratory mouse diet at a final concentration of 1.0% 9 days before irradiation and 30 days thereafter or dissolved in corn oil and administered transorally. Accumulated amounts of coenzyme Q10 (CoQ10) or coenzyme Q9 in the intestine were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), apoptosis, and morphologic changes in the intestine were assessed by immunohistochemistry after administration of 13 Gy of x-ray to the mouse abdomen. Body weight and survival were monitored for 30 days after irradiation. Cytotoxicity using 3 human cancer cell lines and the tumor growth–inhibiting effect in a xenograft were investigated to determine whether rCoQ10 interferes with radiation-specific cytotoxic effects on tumor growth. RESULTS: CoQ10 was greatly accumulated in all sections of the intestine after both massive transoral dosing and dietary administration, whereas coenzyme Q9 was not. Administration of rCoQ10 suppressed ROS production and inhibited apoptosis in the crypts, resulting in preservation of villi structures after irradiation. Notably, 92% of mice fed the rCoQ10-supplemented diet were healthy and alive 30 days after irradiation, whereas 50% of control mice died (P < .05). Moreover, rCoQ10 did not interfere with radiation-specific cytotoxic effects on tumors either in vitro or in vivo. CONCLUSIONS: Administration of rCoQ10 led to its accumulation in the intestine and induced radioprotective effects by inhibiting ROS-mediated apoptosis, thereby preserving intestinal structures. Our results indicated that rCoQ10 supplementation effectively ameliorated radiation enteropathy.
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spelling pubmed-64603182019-04-22 Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10 Shimizu, Yasuyuki Mukumoto, Naritoshi Idrus, Nelly Akasaka, Hiroaki Inubushi, Sachiko Yoshida, Kenji Miyawaki, Daisuke Ishihara, Takeaki Okamoto, Yoshiaki Yasuda, Takahiro Nakahana, Makiko Sasaki, Ryohei Adv Radiat Oncol Biology Contribution PURPOSE: Effective methods to ameliorate radiation enteropathy have not been developed. To address this issue, we investigated the reduced form of coenzyme Q10 (rCoQ10) as a potential radioprotector in a mouse model. METHODS AND MATERIALS: rCoQ10 was added to a standard laboratory mouse diet at a final concentration of 1.0% 9 days before irradiation and 30 days thereafter or dissolved in corn oil and administered transorally. Accumulated amounts of coenzyme Q10 (CoQ10) or coenzyme Q9 in the intestine were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), apoptosis, and morphologic changes in the intestine were assessed by immunohistochemistry after administration of 13 Gy of x-ray to the mouse abdomen. Body weight and survival were monitored for 30 days after irradiation. Cytotoxicity using 3 human cancer cell lines and the tumor growth–inhibiting effect in a xenograft were investigated to determine whether rCoQ10 interferes with radiation-specific cytotoxic effects on tumor growth. RESULTS: CoQ10 was greatly accumulated in all sections of the intestine after both massive transoral dosing and dietary administration, whereas coenzyme Q9 was not. Administration of rCoQ10 suppressed ROS production and inhibited apoptosis in the crypts, resulting in preservation of villi structures after irradiation. Notably, 92% of mice fed the rCoQ10-supplemented diet were healthy and alive 30 days after irradiation, whereas 50% of control mice died (P < .05). Moreover, rCoQ10 did not interfere with radiation-specific cytotoxic effects on tumors either in vitro or in vivo. CONCLUSIONS: Administration of rCoQ10 led to its accumulation in the intestine and induced radioprotective effects by inhibiting ROS-mediated apoptosis, thereby preserving intestinal structures. Our results indicated that rCoQ10 supplementation effectively ameliorated radiation enteropathy. Elsevier 2019-01-31 /pmc/articles/PMC6460318/ /pubmed/31011668 http://dx.doi.org/10.1016/j.adro.2019.01.006 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Biology Contribution
Shimizu, Yasuyuki
Mukumoto, Naritoshi
Idrus, Nelly
Akasaka, Hiroaki
Inubushi, Sachiko
Yoshida, Kenji
Miyawaki, Daisuke
Ishihara, Takeaki
Okamoto, Yoshiaki
Yasuda, Takahiro
Nakahana, Makiko
Sasaki, Ryohei
Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10
title Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10
title_full Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10
title_fullStr Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10
title_full_unstemmed Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10
title_short Amelioration of Radiation Enteropathy by Dietary Supplementation With Reduced Coenzyme Q10
title_sort amelioration of radiation enteropathy by dietary supplementation with reduced coenzyme q10
topic Biology Contribution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460318/
https://www.ncbi.nlm.nih.gov/pubmed/31011668
http://dx.doi.org/10.1016/j.adro.2019.01.006
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