Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats

Pueraria candollei var. mirifica (Fabaceae) root (PMR) has recently been developed as a potential selective estrogen receptor modulator (SERM) in menopausal women. Nowadays, many premenopausal women also take dietary PMR supplements, however, the exact biological effects of PMR have not been evaluat...

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Main Authors: Mallika Srasri, Prayook Srivilai, Panida Loutchanwoot
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:Toxicology Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214750022001962
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author Mallika Srasri
Prayook Srivilai
Panida Loutchanwoot
author_facet Mallika Srasri
Prayook Srivilai
Panida Loutchanwoot
author_sort Mallika Srasri
collection DOAJ
description Pueraria candollei var. mirifica (Fabaceae) root (PMR) has recently been developed as a potential selective estrogen receptor modulator (SERM) in menopausal women. Nowadays, many premenopausal women also take dietary PMR supplements, however, the exact biological effects of PMR have not been evaluated. This study included the application of the OECD guideline 407 for the assessment of 28-day oral exposure to PMR on pituitary-ovarian (PO) axis function and metabolic parameters in the premenopausal rat model. Ovary-intact adult rats were orally administrated with 10, 100, 750, 1000, and 1500 mg/kg body weight (BW)/day of PMR powder. The positive estrogenic group was given 2 mg 17β-estradiol (E2)/kg BW/day. Serum levels of reproductive hormones, lipid and thyroid parameters, estrous cycle determination, and histomorphometric and histopathological evaluations of the anterior pituitary, ovary, uterus, vagina, mammary gland, and liver were investigated. PMR displayed neutral effects on uterine, vaginal, and body weights, and circulating E2 and prolactin levels. PMR exerted E2-like effects by i) reducing ovarian and increasing hepatic weights, ii) decreasing serum gonadotropins, iii) lowering serum lipids without altering thyroid parameters, iv) increasing the prevalence of abnormal estrous cycles with prolonged estrus, v) increasing nuclear diameter of anterior pituitary cells, vi) decreasing ovarian size and follicular numbers and increasing follicular degeneration, vii) thickening of uterine myometrium and luminal epithelium, and vaginal epithelium, and viii) induction of mammary alveolar hyperplasia and ductal secretion. Unlike E2, the appearance of very small numbers of focal microvesicular steatosis in hepatocytes demonstrated mild toxicity at high PMR doses. This is the first report that high-dose PMR exerted actions exactly like E2 on gonadotrope-ovarian axis function and histology, lipid, and thyroid parameters without affecting uterine and vaginal growth in ovary-intact rats according to OECD guidelines.
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spelling doaj.art-0025b8c7779c49678df3ad3dbbe919c62022-12-22T03:00:50ZengElsevierToxicology Reports2214-75002022-01-01918311845Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact ratsMallika Srasri0Prayook Srivilai1Panida Loutchanwoot2Department of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandDepartment of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandCorrespondence to: Department of Biology, Faculty of Science, Mahasarakham University, Kantharawichai District, Maha Sarakham Province 44150 Thailand.; Department of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandPueraria candollei var. mirifica (Fabaceae) root (PMR) has recently been developed as a potential selective estrogen receptor modulator (SERM) in menopausal women. Nowadays, many premenopausal women also take dietary PMR supplements, however, the exact biological effects of PMR have not been evaluated. This study included the application of the OECD guideline 407 for the assessment of 28-day oral exposure to PMR on pituitary-ovarian (PO) axis function and metabolic parameters in the premenopausal rat model. Ovary-intact adult rats were orally administrated with 10, 100, 750, 1000, and 1500 mg/kg body weight (BW)/day of PMR powder. The positive estrogenic group was given 2 mg 17β-estradiol (E2)/kg BW/day. Serum levels of reproductive hormones, lipid and thyroid parameters, estrous cycle determination, and histomorphometric and histopathological evaluations of the anterior pituitary, ovary, uterus, vagina, mammary gland, and liver were investigated. PMR displayed neutral effects on uterine, vaginal, and body weights, and circulating E2 and prolactin levels. PMR exerted E2-like effects by i) reducing ovarian and increasing hepatic weights, ii) decreasing serum gonadotropins, iii) lowering serum lipids without altering thyroid parameters, iv) increasing the prevalence of abnormal estrous cycles with prolonged estrus, v) increasing nuclear diameter of anterior pituitary cells, vi) decreasing ovarian size and follicular numbers and increasing follicular degeneration, vii) thickening of uterine myometrium and luminal epithelium, and vaginal epithelium, and viii) induction of mammary alveolar hyperplasia and ductal secretion. Unlike E2, the appearance of very small numbers of focal microvesicular steatosis in hepatocytes demonstrated mild toxicity at high PMR doses. This is the first report that high-dose PMR exerted actions exactly like E2 on gonadotrope-ovarian axis function and histology, lipid, and thyroid parameters without affecting uterine and vaginal growth in ovary-intact rats according to OECD guidelines.http://www.sciencedirect.com/science/article/pii/S2214750022001962Pituitary-ovarian axisLipid and thyroidMammary glandLiverHistomorphometric analysisEndocrine Disruptor
spellingShingle Mallika Srasri
Prayook Srivilai
Panida Loutchanwoot
Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats
Toxicology Reports
Pituitary-ovarian axis
Lipid and thyroid
Mammary gland
Liver
Histomorphometric analysis
Endocrine Disruptor
title Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats
title_full Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats
title_fullStr Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats
title_full_unstemmed Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats
title_short Assessment of 28-day oral exposure to Pueraria candollei var. mirifica (Fabaceae) roots on pituitary-ovarian axis function and selected metabolic parameters in ovary-intact rats
title_sort assessment of 28 day oral exposure to pueraria candollei var mirifica fabaceae roots on pituitary ovarian axis function and selected metabolic parameters in ovary intact rats
topic Pituitary-ovarian axis
Lipid and thyroid
Mammary gland
Liver
Histomorphometric analysis
Endocrine Disruptor
url http://www.sciencedirect.com/science/article/pii/S2214750022001962
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