title: 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.affiliation: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kochi
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Baba
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sumi
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000097:blood; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000473:pathology*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011230:Precancerous Conditions; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011924:Rats, Zucker; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D002273:Carcinogens; D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D001397:Azoxymethane