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Long-Term Supplementation of Canthaxanthin Does Not Inhibit Gastric Epithelial Cell Proliferation in Helicobacter mustelae-Infected Ferrets^1,2,3,

Jing Yu^*, James G. Fox, Michael C. Blanco, Lili Yan, Pelayo Correa and Robert M. Russell^*,4

^* Gastrointestinal Nutrition Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139 Department of Pathology, Louisiana State University Medical Center, New Orleans, LA 70112

The effect of canthaxanthin (CX), a non-provitamin A carotenoid, on gastric epithelial proliferation was studied in ferrets colonized with Helicobacter mustelae, which causes a chronic gastritis and an increased gastric epithelial cell proliferation. Seven spayed female ferrets were dosed by gavage with CX beadlets (50 mg/kg body wt, 5 d/wk) over 2 y, whereas seven control animals were given placebo beadlets. At the end of the 2-y-period, ferrets were killed, and gastric tissues were obtained from the antrum and body regions. A cell-proliferating biomarker, proliferating cell nuclear antigen (PCNA), was assayed by immunohistochemistry. The PCNA positivity was measured by a computer-based image analysis system. Serum concentrations of carotenoids, retinoids and tocopherols were analyzed by HPLC. Serum antioxidant status was measured by the oxygen radical absorbance capacity (ORAC) assay. The PCNA positivity in both antrum and body regions was not significantly different between CX-fed ferrets and controls. Serum CX concentrations were significantly higher in CX-fed ferrets vs. controls (P<0.001), whereas levels of other carotenoids, retinoids and tocopherols were not significantly different. The ORAC values were not significantly different between groups. This study does not suggest inhibitory effects of CX on gastric epithelial cell proliferation in H. mustelae infected ferrets.

KEY WORDS: • canthaxanthin • proliferating cell nuclear antigen • Helicobacter mustelae • ferrets • gastritis

¹ Funded in part by a grant from Hoffmann-La Roche, Inc. and federal funds from the U.S. Department of Agriculture, Agricultural Research Service, under contract 53-3K06-01 and NIH grants RR010146 and RR07036.

² The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed at: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111.

Manuscript received 6 March 1995. Revision accepted 9 June 1995.