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Soy isoflavones prevent ovariectomy-induced atherosclerotic lesions in Golden Syrian hamster model of postmenopausal hyperlipidemia

Lucas, Edralin A. PhD1; Lightfoot, Stanley A. MD2; Hammond, Lisa J. RD, MS1; Devareddy, Latha MS1; Khalil, Dania A. RD, PhD1; Daggy, Bruce P. PhD1; Soung, Do Y. MS1; Arjmandi, Bahram H. RD, PhD1

doi: 10.1097/01.GME.0000051509.84118.FD

Objective Soy isoflavones, as dietary supplements, may reduce the formation of atherosclerotic lesions that increase in women after menopause. The objectives of this study were to determine whether (1) ovariectomized (ovx) hamsters will develop atherosclerotic lesions and (2) soy isoflavones can dose-dependently prevent the ovariectomy-induced rise in plasma cholesterol and atherosclerotic lesions in hamsters.

Design Seventy-two 6-month-old female Golden Syrian hamsters were randomly assigned to six groups: sham-operated; ovx control; ovx + 17β-estradiol (E2; 10 μg E2 per kilogram of body weight); and ovx + 9.5 (low-dose), 19 (medium-dose), or 38 (high-dose) mg isoflavones per kilogram diet. Treatments were initiated immediately after surgery and continued for 120 days. Blood was drawn via abdominal aorta for assessment of circulating lipids, and tissues were collected, including the aortic arch for assessment of atherosclerotic lesions.

Results All three doses of isoflavones prevented the rise in plasma total cholesterol from ovx; and, as the isoflavone dose increases, the cholesterol-lowering effects of isoflavones become more pronounced (7.8%, 11.8%, and 19.6% reductions in total cholesterol for low-dose, medium-dose, and high-dose, respectively). Ovx hamsters developed atherosclerotic lesions without being on an atherogenic diet. Ninety-two percent of hamsters in the ovx control group had atherosclerotic lesions compared with only 8% in sham, 62% in the E2 group, 29% in the low-dose group, 38% in the medium-dose group, and 58% in the high-dose group. The aortic fatty streak area was approximately 20 times higher in ovx hamsters compared with the sham animals. All doses of isoflavones were able to significantly reduce fatty streak area to that of the sham group.

Conclusions Soy isoflavones, independent of the protein source, prevent hypercholesterolemia and the formation of atherosclerotic lesions induced by ovarian hormone deficiency in hamsters. The antiatherogenic mechanisms of isoflavones need further investigation.

From the 1Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, and the 2Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

Received August 19, 2002; revised and accepted November 21, 2002.

Supported by the Oklahoma Center for the Advancement of Science and Technology; project HR 98-038.

Address reprint requests to Bahram H. Arjmandi, Department of Nutritional Sciences, 416 Human Environmental Sciences; Oklahoma State University, Stillwater, OK 74078. E-mail:

©2003The North American Menopause Society