The Possible Effect of Flaxseed Extract on Letrozole-Induced Polycystic Ovary Rat Model: Correlative Histological and Functional Study

Abstract

Background: Polycystic Ovary Syndrome (PCOS) is one of the most common metabolic disorders affecting women in the reproductive age leading to infertility/subfertility. It may occur as a complication of Letrozole (LTZ) therapy in breast cancer patients.Objective: This was a preliminary study to assess the possible protective and/or curative effect of flaxseed extract in a letrozole-induced PCO rat model. Material and Methods:Thirty-six adult female albino rats were divided into five main groups: Group I kept as the control group, Group II (Letrozole-induced PCO group), received letrozole solution (3 mg/kg) orally once daily by gastric tube for 21 days. Group III (combined flaxseed and letrozole group), received aqueous flaxseed extract (500 mg /kg/day) orally one hour before letrozole in the same dose and duration as group II, Group IV (recovery group), received letrozole in the same dose and duration as group II and then left without treatment for the next 4 weeks after PCO induction, Group V (flaxseed-treated group), treated with aqueous flaxseed extract orally once daily for the next 4 weeks after PCO induction. At the end of the experiment, final body weight, ovarian weight, blood glucose, serum antioxidants assay, and sex hormones levels were measured. Also, specimens of ovaries were processed for light and electron microscopic studies. Histomorphometric and statistical analyses were done.Results: letrozole-induced PCO resulted in a significant increase in final body weight, ovarian weight as well as abnormal blood glucose, sex steroids hormone levels, and antioxidant assays. Moreover, numerous ovarian cystic follicles, widespread cytoplasmic vacuolation in the granulosa lutein cells, congested blood capillaries, and increased fibrosis within the ovarian medulla were evident in the PCO group in concomitant with a significant increase in area percentage of collagen fibers. The ultrastructural assessment confirmed these distortions. The protective and curative potential of flaxseed is mostly comparable revealed improvement in MONA M. ABD EL-GALIL AND SHYMAA FATHY MOHAMED 3052 the final body weight, biochemical markers and histological changes, with the protective effect was more pronounced than the curative one. Conclusion and Recommendation:Flaxseed succeeded in ameliorating letrozole-induced polycystic ovary owing to its phytochemicals, antioxidant and anti-inflammatory properties with folliculogenesis potentials. So, it is recommended to use flaxseed as a co-therapy with letrozole to reduce its hyperandrogenic effects.

Study Vitamin D3 Effect on Polycystic Ovarian Induction by Letrozole of Rat

“…The results of our current study showed a significant increase in the body weight of females treated with letrozole, and this result corresponds with the results of Jahan et al [23] who noticed a significant increase in the body weight of rats treated with letrozole at a dose of 1 mg / kg orally for a period of 21 days , and agree with the results of some authors [20] Those who recorded a significant increase in the weight of female rats treated with letrozole at a dose of 3 mg / kg orally for a period of 21 days, Perhaps the reason for the high body weight in our current study is that the letrozole treatment caused high blood glucose, which contributes to the development of insulin resistance [11,12]. In the group treated with letrozole, there was a a significant increase in the ovarian weight, and this result is corresponds with Mohamed and Fathy , 2021 [20]. Those who observed a significant increase in ovarian weight after administering letrozole 3 mg/kg orally for 21 days, and agree with Ibrahim et al [24] those who noticed a significant increase in the ovarian weights when using letrozole at a dose of 1 mg / kg orally for a period of 21 days, the results not agree with Kafali et al, who reported nonsignificant increase in ovarian weight after taking Letrozole at a dosage of 1 mg/kg orally for 21 days.…”

“…The studies found that giving female rats consecutive doses of letrozole disrupted their estrous cycle [22] Furthermore, letrozole use causes a disruption in the secretion of hormones from the pituitary gland and the ovaries, resulting in polycystic ovary syndrome due to hypersecretion of androgens in the blood and ovaries [10]. The results of our current study showed a significant increase in the body weight of females treated with letrozole, and this result corresponds with the results of Jahan et al [23] who noticed a significant increase in the body weight of rats treated with letrozole at a dose of 1 mg / kg orally for a period of 21 days , and agree with the results of some authors [20] Those who recorded a significant increase in the weight of female rats treated with letrozole at a dose of 3 mg / kg orally for a period of 21 days, Perhaps the reason for the high body weight in our current study is that the letrozole treatment caused high blood glucose, which contributes to the development of insulin resistance [11,12]. In the group treated with letrozole, there was a a significant increase in the ovarian weight, and this result is corresponds with Mohamed and Fathy , 2021 [20].…”

“…This result corresponds with a significant increase in lipid peroxidation (malondialdehyde) [22]. The reduction in glutathione and increased malondialdehyde in our current study might be due to an increase in the production of reactive oxygen species caused by letrozole and the development of oxidative stress [20]. The results of the present research also showed a significant increase in the level of luteinizing hormone in the letrozole-treated group, which is similar to previous study [26].…”

“…Letrozole (Accord,United Kingdom) was given orally using a gavage needle at 3mg/kg body weight [20].vitamin D3 (FDC Nutrition United States) was given orally by gavage needle at 1000 IU/Kg body weight [21]. which had all been dissolved in 5% Carboxymethyl cellulosel (CMC).…”

Tracing the pathways and mechanisms involved in medicinal uses of flaxseed with computational methods and bioinformatics tools

“…Flaxseed oil has many health benefits as it has a proper balance of essential fatty acids such as αlinolenic acid (ALA); an omega-3 biological precursor, linoleic acid; an omega-6 fatty acid; and omega-9 fatty acids. Potassium, lecithin, magnesium, 6% mucilage, traces of cyanogenic glycoside linamarin (El-galil and Mohammed, 2021), and vitamins (A, B, D, and E) are present in flaxseed. Flaxseed also includes phytoactive chemicals such as phenolic compounds, terpenoids, pigments, and other naturally occurring antioxidants.…”