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Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice

Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess...

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Autores principales: Fukuta, Kazufumi, Shirakami, Yohei, Maruta, Akinori, Obara, Koki, Iritani, Soichi, Nakamura, Nobuhiko, Kochi, Takahiro, Kubota, Masaya, Sakai, Hiroyasu, Tanaka, Takuji, Shimizu, Masahito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343947/
https://www.ncbi.nlm.nih.gov/pubmed/28212276
http://dx.doi.org/10.3390/ijms18020413
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author Fukuta, Kazufumi
Shirakami, Yohei
Maruta, Akinori
Obara, Koki
Iritani, Soichi
Nakamura, Nobuhiko
Kochi, Takahiro
Kubota, Masaya
Sakai, Hiroyasu
Tanaka, Takuji
Shimizu, Masahito
author_facet Fukuta, Kazufumi
Shirakami, Yohei
Maruta, Akinori
Obara, Koki
Iritani, Soichi
Nakamura, Nobuhiko
Kochi, Takahiro
Kubota, Masaya
Sakai, Hiroyasu
Tanaka, Takuji
Shimizu, Masahito
author_sort Fukuta, Kazufumi
collection PubMed
description Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model.
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spelling pubmed-53439472017-03-16 Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice Fukuta, Kazufumi Shirakami, Yohei Maruta, Akinori Obara, Koki Iritani, Soichi Nakamura, Nobuhiko Kochi, Takahiro Kubota, Masaya Sakai, Hiroyasu Tanaka, Takuji Shimizu, Masahito Int J Mol Sci Article Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model. MDPI 2017-02-15 /pmc/articles/PMC5343947/ /pubmed/28212276 http://dx.doi.org/10.3390/ijms18020413 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fukuta, Kazufumi
Shirakami, Yohei
Maruta, Akinori
Obara, Koki
Iritani, Soichi
Nakamura, Nobuhiko
Kochi, Takahiro
Kubota, Masaya
Sakai, Hiroyasu
Tanaka, Takuji
Shimizu, Masahito
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
title Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
title_full Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
title_fullStr Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
title_full_unstemmed Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
title_short Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
title_sort preventive effects of pentoxifylline on the development of colonic premalignant lesions in obese and diabetic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343947/
https://www.ncbi.nlm.nih.gov/pubmed/28212276
http://dx.doi.org/10.3390/ijms18020413
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