Enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats.

Abstract

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.

• Authors: Takahiro Kochi, Masahito Shimizu, Tomohiko Ohno, Atsushi Baba, Takafumi Sumi, Masaya Kubota, Yohei Shirakami, Hisashi Tsurumi, Takuji Tanaka, Hisataka Moriwaki
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 7 Pg. 14700-11 (Jul 15 2013) ISSN: 1422-0067 [Print] Switzerland
• PMID: 23860206 (Publication Type: Journal Article)

Chemical References

• Carcinogens
• Chemokine CCL2
• Interleukin-6
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Angiotensin II
• Catalase
• Glutathione Peroxidase
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Azoxymethane

Topics

• Adipose Tissue (metabolism)
• Angiotensin II (blood)
• Animals
• Azoxymethane (toxicity)
• Carcinogens (toxicity)
• Catalase (genetics, metabolism)
• Chemokine CCL2 (genetics, metabolism)
• Colorectal Neoplasms (pathology)
• Cyclooxygenase 2 (blood)
• Glutathione Peroxidase (genetics, metabolism)
• Hypertension (pathology)
• Insulin Resistance
• Interleukin-6 (blood)
• Intestinal Mucosa (metabolism)
• Male
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Oxidative Stress (drug effects)
• Precancerous Conditions
• RNA, Messenger (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Rats, Zucker
• Tumor Necrosis Factor-alpha (blood, genetics, metabolism)