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Open AccessArticle

Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats

1
Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
2
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(7), 14700-14711; https://doi.org/10.3390/ijms140714700
Received: 2 May 2013 / Revised: 25 June 2013 / Accepted: 27 June 2013 / Published: 15 July 2013
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
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. View Full-Text
Keywords: hypertension; colon carcinogenesis; oxidative stress; inflammation; angiotensin-II hypertension; colon carcinogenesis; oxidative stress; inflammation; angiotensin-II
MDPI and ACS Style

Kochi, T.; Shimizu, M.; Ohno, T.; Baba, A.; Sumi, T.; Kubota, M.; Shirakami, Y.; Tsurumi, H.; Tanaka, T.; Moriwaki, H. Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats. Int. J. Mol. Sci. 2013, 14, 14700-14711.

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