Park Dong-Heon;Jang Hyun-Yong;Kim Choung-Ik;Cheong Hee-Tae;Park Coon-Keun;Yang Boo-Keun
Toxicological Research
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v.21
no.2
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pp.161-165
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2005
Bisphenol A (SPA), a environmental endocrine disruptor, is considered to bind to estrogen receptors and to regulate the expressions of estrogen responsive genes. This study was to evaluate the effect of SPA administration on body weight, sex ratio and litter size on 18 days in prenatal periods, the effect of reproductive organ weight and blood hematological values on 24 days postpartum in pregnant mice. The female mice was administrated to low doses of SPA (0, 0.05, 0.5 and 5.0 mg/kg B.W.) by intraperitoneal injection in gestation days $0\~15$ with 5 times at 3 days interval. The maternal body weight, litter size and sex ratios were similar to in all experimental groups, but body weights of male and female offspring was significantly lower in 5.0mg SPA group when compared to any other groups (P<0.05). No treatment-related effects on body weight, ovary weight and blood hematological values were observed in dams on 24 days after delivery. The uterine weight in 5.0mg SPA group was slightly higher than those of any other groups, but not significantly difference. The histological evaluation of ovary in dam mice on 24 days after dilivery was not difference in all experimental groups, but the endometriosis of uterus in dam mice were significantly increased in 0.5mg SPA group when compared to control group. These results indicates that low concentration of SPA should not be considered as a selective reproductive toxicant.
This study was conducted to find out the effects of estrogen and progesterone on body weight, uterine weight and serum prolactin levels on the growing female rats which were ovariectomized. For this purpose, 125 heads of rats (Wistar-Imamichi strain), 28 days old, were devided into 5 groups; OVariectomy(Ovx.), ovariectomy treated with estrogen(Ovx.+Est.), ovariectomy treated with progesterone(Ovx.+Prog.), ovariectomy treated with estrogen and progesterone(Ovx.+Est.+Prog.) and control group. Twenty-five heads of rats were arranged to each group, and changes of body weights were weekly checked. On the other hand, every 5 heads of rats in each group were sacrificed at 1, 2, 3, 4 and 5 weeks after treatments with time elapse for measuring concentrations of serum prolactin and for investigating the weights of ulterus. Prolactin concentrations in the serum were analyzed by radioimmunoassay. The results obtained are as follows; 1. The body weights were increased slightly in Ovx. in comparison with Ovx.+Prog., Ovx.+Est.+Prog., Ovx.+Est. and control groups, but there were not significant among the compared groups at all observation times. 2. The uterine weights in all treatment groups were decreased significantly (P<0.01) compared with control groups at all observation times. But the weights in Ovx. and Ovx.+Prog. groups were lower than those in Ovx.+Est. and Ovx.+Est.+Prog.. 3. Serum prolactin concentrations were increased slightly in control group in comparison with other groups at 1 and 2 weeks increased slightly in control group in comparison with other groups at 1 and 2 weeks after treatment. But compared with control group, the concentrations Ovx.+Est. and Ovx.+Est.+Prog. were high level, and those in other groups were low level in the order of Ovx. and Ovx.+Prog. groups at 3, 4 and 5 weeks after treatment. There were not significant among the compared groups at all observation times. 4. The results obtained in this study suggest that when ovariectomized rats receive 1$\mu$g estrogen and 3mg progesterone daily, that had no effect on body weight and serum prolactin concentrations while significantly effect on the weight of uterus.
Objectives : This study was carried out to determine the effects of Gamidokwalgisaeng-tang(GDS) oral administration and electro-acupuncture at $BL_{52}$ & $GB_{39}$ on the postmenopausal osteoporosis. Methods: In order to study the effects of the Gamidokwalgisaeng-tang(GDS) oral administration and electro-acupuncture at $BL_{52}$, $GB_{39}$ on osteoporotic rats induced by ovariectomy, body weight, femur weight, uterine weight, serum level of osteocalcin, alkaline phosphatase(ALP), cholesterol, triglyceride, estradiol, androstenedione, testosterone and urinary excretions of calcium & phosphorus were measured. Results : 1. Body weight in all experimental group decreased significantly in comparison with ovariectomized group(OVX). 2. The weight of femur compared with body increased significantly in GDS oral administration and combination treatment group in comparison with ovariectomized group(OVX). 3. Uterine endometrial morphology is caused by ovariectomy and the weight of uterus decreased significantly in control and all experimental group in comparison with sham. 4. The serum level of osteocalcin decreased in all experimental group in comparison with OVX, but significantly in electro-acupuncture and combination treatment group. 5. The serum alkaline phosphatase(ALP) activity decreased in electro-acupuncture and combination treatment group in comparison with OVX, but only significantly in electro-acupuncture group. 6. The serum level of cholesterol increased significantly in OVX in comparison with sham and decreased in all experimental group in comparison with OVX, not insignificantly. The serum level of triglyceride increased in all experimental group in comparison with OVX, not insignificantly. 7. Urinary excretions of calcium and phosphorus decreased significantly in all experimental group in comparison with OVX. Conclusion : We suggest that GDS oral administration and electro-acupuncture at $BL_{52}$ & $GB_{39}$ are available for prevention and curing about the postmenopausal osteoporosis.
Journal of Physiology & Pathology in Korean Medicine
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v.24
no.1
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pp.134-142
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2010
Although BinSo-San(BSS), a mixed herbal formula consisted of 11 types of medicinal herbs and have been used as anti-inflammatory agent, In the present study, the acute toxicity (single oral dose toxicity) of lyophilized BSS aqueous extracts was monitored in male and female mice after oral administration according to Korea Food and Drug Administration (KFDA) Guidelines (2005-60, 2005). In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD), maximum tolerance dosage (MTD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines (2005-60, 2005). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines (2005-60, 2005) with organ weight and histopathology of 12 types of principle organs. We could not find any mortality, clinical signs and changes in the body weights except for dose-independent increases of body weight and gains restricted in 1000 mg/kg of BSS extracts-dosing female group. Hypertrophic changes of lymphoid organs.thymus, spleen and popliteal lymph nodes were detectedat postmortem observation with BSS extracts dose-dependent increases of lymphoid organ weights, and hyperplasia of lymphoid cells in these all three lymphoid organs at histopathological observations. These changes are considered as results of pharmacological effects of BSS extracts or their components, immunomodulating effects, not toxicological signs. In addition, some sporadic accidental findings such as congestion spots, cyst formation in kidney, atrophy of thymus and spleen with depletion of lymphoid cells, and edematous changes of uterus with desquamation of uterus mucosa as estrus cycles were detected throughout the whole experimental groups including both male and female vehicle controls. The significant (p<0.01) increases of absolute weights of kidney and pancreas detected in BSS extracts 1000 mg/kg-treated female group are considered as secondary changes from increases of body weights. The results obtained in this study suggest that the BSS extract is non-toxic in mice and is therefore likely to be safe for clinical use. The LD50 and ALD of BSS aqueous extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. In addition, the MTD of BSS extracts was also considered as over 2000 mg/kg because no BSS extracts-treatment related toxicological signs were detected at histopathological observation except for BSS or their component-related pharmacological effects, the immunomodulating effects detected in the present study.
Objective : This study was undertaken to investigate the effects of Eucommiae Cortex on the osteoporosis in ovariectomized rats. Materials and Methods : We used Sprague-Dawley female rats in 8-week-old. They were divided into three groups. Sample group was ovariectomized and administered with 10 mg/100 g/day Eucommiae Cortex extract solution for 10 weeks. Control group was ovariectomized and sham group was conducted by sham's operation. And control group and sham group were administered with normal saline as the same way. We measured rats's body and uterus weight and also measured the serum levels of Ca, phosphorus and ALP. We stained the specimens of rat's tibial bones with Goldner's modified Masson's Trichrome and then examined bone histomorphometry with Bioquant computer program of image analysis system. We measured the thickness of osteoid and callus as static parameters and measured bone volume and mineral apposition rate as dynamic parameters. We observed the expressions of RANKL and OPG mRNA of the tibial bone by RT-PCR. Results : The body weight was significantly (p<0.05) increased in control and sample groups compared with sham group, respectively. The uterus weight was significantly (p<0.05) decreased in control and sample group compared with sham group. In the change of Ca, phosphorus and ALP there were no significant changes among three groups. There were no significant changes of trabecula cortical and osteoid bones' thickness and volume. But trabecula mineral apposition rate (MAR) was significantly (p<0.05) increased in sham and sample group compared with control group. In the expression of RANKL mRNA, sample group was decreased compared with control group, and in that of OPG mRNA, sample group was increased compared with control group. Conclusion : This study shows that Eucommiae Cortex has the beneficial effects on bone histomorphometry and metabolism in the ovariectomized rats. We suggest that Eucommiae Cortex be useful for the treatment of osteoporosis.
Objective: To elucidate 1) whether there are any differences in the urine concentrations of steroid hormone metabolites between patients with leiomyoma and normal controls 2) the correlation between urinary profiles of steroid hormones and leiomyomas of the uterus according to their type, location, volume, and weight. Materials of Methods : The study population consisted of 37 premenopausal patients with uterine leiomyoma and the control group consisted of 25 premenopausal normal volunteer women without uterine leiomyoma. Confirmation of the existence of uterine leiomyoma was done by ultrasonography and histopathological examination after surgery. The volume of the leiomyoma was estimated by trans-abdominal and/or trans-vaginal ultrasonography. The Leiomyomas were divided into 3 types (subserosal, intramural and submucosal). Seventeen patients had subserosal type of leiomyoma, 10 with the intramural type and 10 with the submucosal type. The locations of the leiomyoma were also divided into 3 groups (fundus, body and isthmus). Seventeen patients showed a fundus location, 10 in body, and 10 in isthmus. We compared urinary profiles of the endogenous steroids between patients with leiomyomas and normal controls, and also investigated the relationship between urinary profiles of the endogenous steroids and leiomyomas according to their type, location, volume and weight by using highly sensitive Gas Chromatography-Mass Spectrometry (GC-MS) system. Results: The mean ages of the patients with leiomyomas and the control group were $43.1{\pm}5.6$ and $40.6{\pm}7.2$ years, the weights were $63.4{\pm}7.3$ and $59.4{\pm}8.1\;kg$, and their heights were $155.4{\pm}4.8$ and $159.3{\pm}4.8\;cm$ respectively. Seventeen patients had subserosal, 10 had intramural, and 10 had submucosal leiomyomas. There were 17 patients with leiomyoma located in fundus, 10 in body and 10 in isthmus. $17{\beta}$-estradiol, 5-AT, 11-keto ET, $11{\beta}$-hydroxy An, $11{\beta}$-hydroxy Et, THS, THA, THE, a-cortolone, a-cortol, $\beta$-cortol, $11{\beta}$-OH Et/$11{\beta}$-OH An and E2/E1 were significantly increased in patients with leiomyoma than in the control group. $17{\beta}$-estradiol was significantly increased in the intramural and the submucosal types than in the subserosal type. There was no significant difference in the concentrations of urinary steroids according to the locations of leiomyomas. There was no significant relationship between the concentration of urinary steroids and the volume of the leiomyomas. $17{\beta}$-estradiol significantly decreased as the weight of uterus increased (r=-0.322, p=0.04). Conclusion: The concentrations of steroid hormone metabolites were generally increased in patients with leiomyoma but were not significantly related to the volume and weight of the leiomyomas. Our study suggests that steroid hormones may be involved in the initiation of leiomyomas but may not be involved in their progression. In addition, the concentrations of steroid hormone metabolites are not related to the leiomyoma type and location.
Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.
Yahi, Dauda;Ojo, Nicholas Adetayo;Mshelia, Gideon Dauda
Journal of Animal Science and Technology
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v.59
no.5
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pp.12.1-12.7
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2017
Background: Despite the widespread use of dexamethasone in veterinary and human medicine, it is reported to cause some severe pregnancy related side effects like abortion in some animals. The mechanism of the response is not clear but seems to be related to interspecies and/or breed difference in response which may involve alterations in the concentrations of some reproductive hormones. Methods: Twenty Sahel goats comprising 18 does and 2 bucks were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injections were given at 0.25 mg/kg body weight. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested at days 28 and day 78 of gestation through caesarean section for immunohistochemical analysis using 3 pregnant does randomly selected from each group at each instant. Data were expressed as Means ${\pm}$ Standard Deviations and analyzed using statistical soft ware package, GraphPad Instant, version 3.0 (2003) and progesterone receptor (PR) were scored semi-quantitatively. Results: Dexamethasone treatments had no significant (p > 0.05) effect on progesterone and estrogen concentrations in pregnant Sahel goats but up regulated PR from 2+ to 3+ in second trimester. Conclusion: As dexamethasone adverse effect on placenta is an established fact, the lack of effect on progesterone level in this study may be due to the fact that unlike other species whose progesterone production during pregnancy is placenta - dependent, in goats is corpus luteum - dependent. Consequently dexamethasone adverse effect on placenta reported in literatures did not influence progesterone levels during pregnancy in Sahel goat. The up regulation of progesterone receptor (PR) in Sahel goat gravid uterus is a beneficial effects and that dexamethasone can safely be used in corpus luteum - dependent progesterone secreting pregnant animal species like Sahel goat and camel. Therefore source of progesterone secretions during pregnancy should be considered in clinical application of dexamethasone in pregnancy.
Horses that have been retired from racing or imported from abroad are retired as broodmares. Whether at private farms or government institutes they are bred to stallions with the aim of improving fertility and enhancing the breed. Accidental deaths as a result of surgical or obstetrical complications lead to decreased productivity and economic losses to the horse breeding industry. Intussusception of the uterine horn is a frequent complication of the equine and bovine species, but rarely seen in other species. The most common causes are thought to be tearing of the placenta which is suspended from the uterus and ovaries and the weight of the placenta. Expulsion of the embryonic membranes is also thought to be a contributing factor. If symptoms are minor and treatment affected quickly, the problem will likely resolve itself. In more severe cases the uterus will prolapse completely. This case study was observed in a Thoroughbred broodmare. After treatment of dystocia, the broodmare could not stand up. She became dehydrated, collapsed, suffered colic and was euthanised. In this case was observed serious swelling vulva and perineal region by morphology, and there was seldom ascites and unusual view in thoracic and abdominal cavity after opening abdomen. However, intussusception of uterine horn involuted left uterine horn into the uterine body was observed.
The seed powder of Abrus precatorius L. has traditionally been used as oral contraceptive agent by the women in some rural areas in Bangladesh. The present study aimed to examine the antifertility activity of A. precatorius seed extracts in experimental female rats. Finely ground seeds were extracted with aqueous acetone followed by successive partitioning with n-hexane, ethyl acetate (EtOAc), methanol (MeOH) and water. Water suspended crude seed powder, organic fractions of acetone extract and a standard contraceptive drug ($Nordette^{(R)}28$) were separately administered orally to the female rats for 30 days. n-Hexane, EtOAc and MeOH solubles at the doses of 2, 4 and 6 mg/rat/day, respectively and crude seed powder at 100 mg/rat/day exhibited 100% antifertility activity with lowest levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and $17{\beta}$-estradiol. Histological study of ovary and uterus of these rats exhibited reduced number of developing follicles and increased number of atretic follicles in the ovary, and fewer uterine glands with shrunken morphology, reduced endometrial height, poor vascularity and compact stroma in uterus. However, the activities of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase and the body weight of the rats remained almost unaffected in all the seed extract treated rats compared to control. These results suggest that A. precatorius seed extracts reduced the levels of serum FSH, LH and $17{\beta}$-estradiol probably by affecting hypothalamic-pituitary-gonadal axis. The reduced levels of these hormones might have affected the oestrous cycle, follicular development, and subsequently the establishment of pregnancy in treated rats.
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