Abstract:
:Metabolic syndrome (Mets), including diabetes and hypertension, increases the risk of colorectal cancer via the induction of chronic inflammation, acceleration of oxidative stress, and activation of the renin-angiotensin system. The present study examined the possible inhibitory effects of captopril, an angiotensin-converting enzyme (ACE) inhibitor and antihypertensive drug, on the development of azoxymethane (AOM)-induced colonic premalignant lesions, aberrant crypt foci (ACF), in SHRSP.Z-Lepr fa /IzmDmcr (SHRSP-ZF) diabetic and hypertensive rats. Male 6-week-old SHRSP-ZF rats were administered two, weekly intraperitoneal injections of AOM (20 mg/kg body weight). Following the second injection, the rats received drinking water containing captopril (8 mg/kg/day) for two weeks. At sacrifice, captopril administration significantly lowered the blood pressure and reduced the total number and size of ACF compared with those observed in the untreated group. The serum levels of angiotensin-II and the expression levels of ACE and angiotensin-II type 1 receptor mRNA on the colonic mucosa decreased following captopril treatment. Captopril also reduced the urinary 8-hydroxy-2'-deoxyguanosine levels and the serum derivatives of reactive oxygen metabolites levels, both of which are oxidative stress markers, but increased the mRNA levels of catalase, an antioxidant enzyme, in the colonic epithelium. Moreover, the expression levels of tumor necrosis factor-α, interleukin-18, monocyte chemoattractant protein-1, inducible nitric oxide synthase, vascular endothelial growth factor and proliferating cell nuclear antigen mRNA in the colonic epithelium were decreased significantly following captopril administration. These observations suggested that captopril prevents the development of ACF by inhibiting renin-angiotensin system activation and attenuating inflammation and oxidative stress in SHRSP-ZF rats. Therefore, targeting Mets-related pathophysiological conditions, including renin-angiotensin system activation, may be an effective strategy to prevent colorectal carcinogenesis in patients with Mets, particularly those with hypertension.
journal_name
Oncol Lettjournal_title
Oncology lettersauthors
Kochi T,Shimizu M,Ohno T,Baba A,Sumi T,Kubota M,Shirakami Y,Tsurumi H,Tanaka T,Moriwaki Hdoi
10.3892/ol.2014.2136subject
Has Abstractpub_date
2014-07-01 00:00:00pages
223-229issue
1eissn
1792-1074issn
1792-1082pii
ol-08-01-0223journal_volume
8pub_type
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