Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats
Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDm...
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doaj-5187a6aece4549c3a4b8f83166fbf02c2020-11-24T22:30:23ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-07-01147147001471110.3390/ijms140714700Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive RatsTakuji TanakaHisashi TsurumiYohei ShirakamiMasaya KubotaTakafumi SumiAtsushi BabaTomohiko OhnoMasahito ShimizuTakahiro KochiHisataka MoriwakiMetabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.http://www.mdpi.com/1422-0067/14/7/14700hypertensioncolon carcinogenesisoxidative stressinflammationangiotensin-II |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takuji Tanaka Hisashi Tsurumi Yohei Shirakami Masaya Kubota Takafumi Sumi Atsushi Baba Tomohiko Ohno Masahito Shimizu Takahiro Kochi Hisataka Moriwaki |
spellingShingle |
Takuji Tanaka Hisashi Tsurumi Yohei Shirakami Masaya Kubota Takafumi Sumi Atsushi Baba Tomohiko Ohno Masahito Shimizu Takahiro Kochi Hisataka Moriwaki Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats International Journal of Molecular Sciences hypertension colon carcinogenesis oxidative stress inflammation angiotensin-II |
author_facet |
Takuji Tanaka Hisashi Tsurumi Yohei Shirakami Masaya Kubota Takafumi Sumi Atsushi Baba Tomohiko Ohno Masahito Shimizu Takahiro Kochi Hisataka Moriwaki |
author_sort |
Takuji Tanaka |
title |
Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats |
title_short |
Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats |
title_full |
Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats |
title_fullStr |
Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats |
title_full_unstemmed |
Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats |
title_sort |
enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2013-07-01 |
description |
Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system. |
topic |
hypertension colon carcinogenesis oxidative stress inflammation angiotensin-II |
url |
http://www.mdpi.com/1422-0067/14/7/14700 |
work_keys_str_mv |
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