The Ethanol Extract of Avocado (Persea americana Mill. (Lauraceae)) Seeds Successfully Induces Implant Regression and Restores Ovarian Dynamic in a Rat Model of Endometriosis

Abstract

Endometriosis is an estrogen-dependent disease with conventional therapies which do not have desirable effectiveness and possess many side effects. Scientific evidences suggest that medicinal plants with antioxidant, anti-inflammatory, and/or antiproliferative properties are potential alternatives for the treatment of endometriosis. The ethanol extract of Persea americana Mill. (Lauraceae) seeds was found exhibiting antiproliferative properties in vitro and in vivo. This study therefore is aimed at investigating the effects of such an extract on an experimental model of endometriosis. Endometriosis was induced by grafting uterine fragments onto the peritoneum of female Wistar rats. After checking the success of the transplantation surgery, animals with endometriosis were orally treated with the ethanol extract of P. americana seeds at the doses of 12.5, 25, and 50 mg/kg. The positive control was treated with letrozole (10 mg/kg) while the negative control received the vehicle. Treatments lasted 7 days and animals were sacrificed thereafter. Endometrial implant volume was determined. Estradiol and progesterone levels were measured in serum samples and endometriosis lesions. The oxidative status of endometriosis lesions was evaluated. Histological analysis of endometriosis lesions, uterus, and ovaries was also performed. Results showed that the ethanol extract of P. americana seeds decreased endometrial implant volume (p < 0.001) and serum levels of estradiol and progesterone (p < 0.01). The levels of estradiol also decreased in endometriosis lesions at doses of 12.5 and 50 mg/kg (p < 0.001). Both malondialdehyde and glutathione levels increased in endometriosis lesions (p < 0.001). The ectopic endometrium height decreased and the number of antral follicles and corpora lutea (p < 0.05) increased while that of luteinized unruptured follicles decreased (p < 0.001). In conclusion, the ethanol extract of P. americana seeds displayed an antiendometriosis effect suggesting that it could be a potential alternative for the treatment of endometriosis.

Figure 1

Effects of P. americana seeds on serum levels of estradiol (a) and progesterone (b) and tissue levels of estradiol (c). Data are presented as mean ± SEM, n = 5, ^µµµp < 0.001 versus [NORMAL], ^##p < 0.01, ^###p < 0.001 versus [SHAM], and ^∗∗∗p < 0.001 versus [ENDO + DW]. SHAM: sham-operated animals; ENDO: animals with endometriosis; DW: distilled water; LTZ: letrozole; EE: ethanol extract of P. americana seeds.

Figure 2

Eutopic (a) and ectopic (b) endometrial epithelial heights. Data are presented as mean ± SEM, n = 5, ^µµp < 0.01, ^µµµp < 0.001 versus [NORMAL], ^#p < 0.05, ^##p < 0.01 versus [SHAM], and ^∗p < 0.05 versus [ENDO + DW]. SHAM: sham-operated animals; ENDO: animals with endometriosis; DW: distilled water; LTZ: letrozole; EE: ethanol extract of P. americana seeds.

Figure 3

Microphotographs (×100, hematoxylin and eosin staining) of the uterus. L = lumen, E = epithelium, yellow arrow = mitosis, red arrow = necrosis. NORMAL: animals without surgery; SHAM: animals with hemi-ovariectomy; ENDO: animals with endometriosis; DW: distilled water; LTZ: letrozole; EE: ethanol extract of P. americana seeds. (a) NORMAL. (b) SHAM. (c) ENDO + DW. (d) ENDO + LTZ. (e) ENDO + EE12.5. (f) ENDO + EE25. (g) ENDO + EE50.

Figure 4

Microphotographs (×100, hematoxylin and eosin staining) of endometrial implants. E = epithelium, L = lumen, and red arrows = necrosis. ENDO: animals with endometriosis; DW: distilled water; LTZ: letrozole; EE: ethanol extract of P. americana seeds. (a) ENDO + DW. (b) ENDO + LTZ. (c) ENDO + EE12.5. (d) ENDO + EE25. (e) ENDO + EE50.

Figure 5

Microphotographs (×100, hematoxylin and eosin staining) of experimental rat ovaries. CL: corpora lutea; GF: Graafian follicle; LUF: luteinized unruptured follicle; TF: tertiary follicle. . (a) NORMAL. (b) SHAM. (c) ENDO + DW. (d) ENDO + LTZ. (e) ENDO + EE12.5. (f) ENDO + EE25. (g) ENDO + EE50.