The effects of myricitrin and vitamin E against reproductive changes induced by D-galactose as an aging model in female mice: An experimental study

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Myricitrin and vitamin E ameliorated D-galactose-induced aging changes in female mice, improving estrous cycles, sex hormone levels, antioxidant capacity, and tissue histology.

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This experimental study used 72 female NMRI mice treated for 45 days with D-galactose to create an aging/oxidative-stress model, then tested whether myricitrin (5, 10, or 20 mg/kg) given by gavage during the last 28 days could mitigate reproductive changes; vitamin E served as a positive comparator. D-gal impaired the estrous cycle, lowered plasma estrogen and progesterone, increased LH and FSH, and increased uterine/ovarian oxidative stress as reflected by higher MDA and lower total antioxidant capacity (TAC), with histology showing follicular degeneration and uterine endometrial atrophy; the paper reports that myricitrin at 5 mg/kg most consistently improved estrous cycling and reduced MDA while raising TAC, and also increased estrogen and progesterone. Reported caveats include that organ weight/body-weight ratios were not significantly changed and that the study relied on a pharmacologic D-gal aging model rather than natural aging. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match about oxidative-stress impacts on reproductive tissues.

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Abstract

BACKGROUND: Aging is accompanied by decreasing general function in the cells and tissues. D-galactose (D-gal) induces aging and plays a role in the pathogenesis of it. Myricitrin is a plant-derived antioxidant. OBJECTIVE: The present study was performed to evaluate the effects of myricitrin on antioxidant defense, sex hormone levels, uterus, and ovarian histology in D-gal-induced aging female mouse model. MATERIALS AND METHODS: In this experimental study, 72 female adult NMRI mice, weighing 30-35 gr, 3-4 months old, were randomly divided into six groups (n = 12/each): (I) Control (vehicle; normal saline), (II) D-gal at 500 mg/kg/d for 45 days, (III-V) D-gal + myricitrin-treated groups (these groups received myricitrin at 5, 10, and 20 mg/kg/d, and (VI) D-gal + 100 mg/kg/d vitamin E orally for the last 28 days. The antioxidant indices were done on the basis of colorimetric method, and sex hormone levels were measured by using enzyme-linked immunosorbent assay kits. Histological assessment of the uterus and ovaries were also evaluated. RESULTS: D-gal impaired the estrous cycle, also degenerative changes occur in the ovarian follicles and damage to the uterus and ovarian tissue occurs. In D-gal group, the level of sex hormones (p = 0.03) and the total antioxidant capacity (p = 0.002) decreased, while the level of malondialdehyde and gonadotropins increased (p = 0.03). Myricitrin at lower doses and vitamin E ameliorated the D-gal effects. CONCLUSION: These findings suggest that myricitrin at low doses can effectively prevent D-gal-induced oxidation and aging in mice. The effect of myricitrin was equivalent and sometimes better than vitamin E.
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Section

This research showed that D-gal by inducing oxidative stress creates a model of aging similar to the normal female reproductive system and reduces fertility. Our results showed that myricitrin in low doses can delay the aging process by increasing secretion of estrogen and progesterone levels, reducing LH, FSH, MDA content and increasing TAC. Myricitrin also had a positive effect on the tissues of the uterus and ovaries. Therefore, myricitrin with the inhibitory effect of oxidative stress in the aging model induced by D-gal, and the suppression of free radicals and ROS, improved the age-related changes in the reproductive system. The minimal studied dose of myricitrin had the highest level of protection compared to other doses. Myricitrin at 20 mg/kg was not toxic but failed to increase the antioxidant potency. These findings suggest that myricitrin can be a candidate to alleviate the age-related changes in women.

Coi Statement

The authors have no conflicts of interest to report with respect to this paper.

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