Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in C57/BL/KsJ-db/dbmice

Abstract

BackgroundObesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis. Astaxanthin, a xanthophyll carotenoid found in aquatic animals, is known to possess antioxidant, anti-inflammatory, and antineoplastic properties. The present study examined the effects of astaxanthin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice.MethodMale db/db mice were administered 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) from 5 weeks of age and subsequently, from 1 week after the last injection of AOM, were fed a diet containing 200 ppm astaxanthin throughout the experiment (8 weeks).ResultThe development of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, was significantly inhibited in mice treated with astaxanthin than in mice fed the basal diet. Astaxanthin administration markedly reduced urinary levels of 8-OHdG and serum levels of d-ROMs, which are oxidative stress markers, while increasing the expression of mRNA for the antioxidant enzymes GPx1, SOD1, and CAT in the colonic mucosa of AOM-treated db/db mice. The expression levels of IL-1β, IL-6, F4/80, CCL2, and CXCL2 mRNA in the colonic mucosa of AOM-treated mice were significantly decreased by astaxanthin. Dietary feeding with astaxanthin also resulted in a reduction in the numbers of NF-κB- and PCNA-positive cells that were increased by AOM exposure, in the colonic epithelium.ConclusionThese findings suggest that astaxanthin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa. Astaxanthin, therefore, may be a potential candidate as a chemoprevention agent against colorectal carcinogenesis in obese individuals.

Astaxanthin and its Effects in Inflammatory Responses and Inflammation-Associated Diseases: Recent Advances and Future Directions

“…In C57BL/6J mice, the mRNA expression of IL-1β, IL-6, TNF-α, IL-36α, and IL-36γ, and the activation of NF-κB, AP-1, and MAPK were suppressed by dietary astaxanthin (Table 2) [68]. In C57BL/KsJ-db/db (db/db) obese mice, astaxanthin inhibited the development of colonic premalignant lesions by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa (Table 2) [37]. Molecules 2020, 25, 5342 7 of 14…”

Antioxidant and Anti-inflammatory Mechanisms of Astaxanthin in Cardiovascular Diseases

“…The increased susceptibility of membrane lipids and low-density lipoprotein (LDL) to oxidation may trigger the formation of thrombi and the development of atherosclerosis [5]. One of the reactive species that induces lipid peroxidation and LDL oxidation is peroxynitrite (ONOO − ) [50,51], which when neutralized by astaxanthin forms 15-nitroastaxanthin, a compound that also has important antioxidant action [52].…”

“…Inflammation plays an important role in the development of cardiovascular diseases and other comorbidities, such as hypertension, hypercholesterolemia, type 2 diabetes, chronic kidney disease, and obesity [50]. Astaxanthin exerts a marked anti-inflammatory effect, which may be interrelated with its antioxidant effect and contributes to physiological changes that benefit cardiovascular function ( Figure 1) [50][51][52][53][54][55].…”

Astaxanthin Prevents Human Papillomavirus L1 Protein Binding in Human Sperm Membranes

“…Asta and H . pluvialis extracts prevents the development of human colon cancer cells by blunting the progression of the cell cycle, ameliorating apoptosis, and suppressing the expression of inflammatory cytokines (e.g., NF-kβ, TNF-a and IL-1β) [ 15 , 16 , 17 , 18 ]. In HCT116 and HT29 cells, Asta induced the expression of the negative regulators of the cell cycle [ 19 ].…”