The ethanol extract of avocado [Persea americana Mill. (Lauraceae)] seeds reduced the hyperplastic effect of tamoxifen on uterine endometrium without changing its effect on the mammary gland

Abstract

Tamoxifen is the most common hormonal treatment for estrogen receptor positive (ER+) breast cancer. However, the long-term use of tamoxifen was associated with increased risks of endometrial cancer. The literature suggests that combining tamoxifen with substances endowed with antiproliferative properties could increase tamoxifen’s chemopreventive benefit. The ethanol extract of Persea americana Mill. (Lauraceae) seeds was found exhibiting antiproliferative properties in vitro. The present study therefore aimed at evaluating the ability of such an extract to prevent tamoxifen-induced endometrial hyperplasia without changing its activity on the mammary gland. This study was performed in ovariectomized rats receiving simultaneously tamoxifen (by the intraperitoneal route) and the ethanol extract of P. americana seeds (by gavage) at doses of 25, 50, 100 and 200 mg/kg. Co-administrations were performed for 37 consecutive days and animals were sacrificed thereafter. Uterine and serum levels of estradiol and cholesterol were assessed. The oxidative status of the uterus was also evaluated. Histology of the uterus and the mammary gland was performed. Results showed that the ethanol extract of P. americana seeds did not alter tamoxifen-induced uterine steroidogenesis but reduced its proliferative effect by decreasing uterine epithelial height (p < 0.001). T his antiproliferative effect was associated with increased uterine levels of malondialdehyde and antioxidant enzymes. On the mammary gland, the non-proliferative effect of tamoxifen was not altered by P. americana extract. In conclusion, the ethanol extract of P. americana seeds could be a complementary treatment to prevent tamoxifen-induced endometrial hyperplasia during the treatment of ER+ breast cancer.