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

Abstract

BACKGROUND:

Obesity 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.

METHOD:

Male 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).

RESULT:

The 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.

CONCLUSION:

These 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.

• Authors: Takahiro Kochi, Masahito Shimizu, Takafumi Sumi, Masaya Kubota, Yohei Shirakami, Takuji Tanaka, Hisataka Moriwaki
• Journal: BMC gastroenterology (BMC Gastroenterol) Vol. 14 Pg. 212 (Dec 17 2014) ISSN: 1471-230X [Electronic] England
• PMID: 25515685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents
• Antioxidants
• Inflammation Mediators
• NF-kappa B
• Xanthophylls
• beta Catenin
• astaxanthine
• Azoxymethane

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Antioxidants (pharmacology, therapeutic use)
• Azoxymethane
• Cell Proliferation (drug effects)
• Colonic Neoplasms (chemically induced, metabolism, prevention & control)
• Inflammation Mediators (metabolism)
• Intestinal Mucosa (drug effects, metabolism)
• Male
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Obesity (complications)
• Oxidative Stress (drug effects)
• Precancerous Conditions (chemically induced, metabolism, prevention & control)
• Xanthophylls (pharmacology, therapeutic use)
• beta Catenin (metabolism)