The therapeutic effect of tissue cultured root of mountain ginseng (Panax ginseng) (tcMG) on 2,3,7,8-tetrachlorodaibenzo-p-dioxin (TCDD) induced toxicity in rat was investigated. The rats were assigned into three groups (10 rats/group), control, TCDD exposed group and tcMG treated group after TCDD exposed. $50\;{\mu}g/kg$ of TCDD was injected by i.p. for TCDD exposed group and 30 mg/kg of tcMG saponin was administered for 4 weeks by oral gavage for tcMG treated group. The weights of body, spleen, kidney, thymus, testes and epididymides were decreased in the single TCDD treatment. However these organs was significantly recovered by tcMG saponin except thymus (p<0.05). tcMG decreased the level of hepatic demage maker enzymes, AST and ALP. It also lowered total cholesterol and triglyceride. The level of serum triglyceride was significantly decreased in tcMG saponin treated group compared with the control. Histopathological examination revealed morphological change in the liver spleen, thymus and testes of TCDD treated rats. However they were relatively well preserved in the tcMG treatment group. In conclusion, TCDD induced toxicity was some repaired by tcMG. tcMG may be useful for prevention and treatment of TCDD induced toxicity.
Inflammaging in male reproductive organs covers a wide variety of problems, including sexual dysfunction and infertility. In this study, the beneficial effects of cordycepin (COR), isolated from potential medicinal fungi Cordyceps militaris, in aging-associated testicular inflammation and serum biochemical changes in naturally aged rats were investigated. Male Sprague Dawley rats were divided into young control (YC), aged control (AC), and COR (5, 10, and 20 mg/kg) treated aged rat groups. Aging-associated serum biochemical changes and inflammatory parameters were analyzed by biochemical assay kits, Western blotting, and real-time RT-PCR. Results showed a significant (p < 0.05) alteration in the total blood cell count, lipid metabolism, and liver functional parameters in AC group when compared with YC group. However, COR-treated aged rats ameliorated the altered biochemical parameters significantly (p < 0.05 and p < 0.01 at 5, 10, and 20 mg/kg, respectively). Furthermore, the increase in the expression of inflammatory mediators (COX-2, interleukin (IL)-6, IL-1β, and tissue necrosis factor-alpha) in aged rat testis was significant (p < 0.05) when compared with YC group. Treatment with COR at 20 mg/kg to aged rats attenuated the increased expression of inflammatory mediators significantly (p < 0.05). Mechanistic studies revealed that the potential attenuating effects exhibited by COR in aged rats was mediated by regulation of NF-κB activation and MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38) signaling. In conclusion, COR restored the altered serum biochemical parameters in aged rats and ameliorated the aging-associated testicular inflammation proving the therapeutic benefits of COR targeting inflammaging-associated male sexual dysfunctions.
Objectives : this study was to access the effect of Hyeonggaeyeongyotang water extracts, a polyherbal formula has been used as folk medicine, on the fertility and early embryonic development of male and female Wistar rats when administered by oral gavage. Methods : In male rats, Hyeonggaeyeongyotang extract were dosed 4 weeks before pairing and 2 weeks after mating including the mating periods up to termination after necropsy of the majority of the females. In female rats, they were dosed 2 weeks before pairing, and from Day 0 to Day 7 of gestation. This study was conducted in accordance with the recommendations of the KFDA Guideline [2005-60] for Detection of Toxicity to Reproduction for Medicinal Products. Results: 1. No Hyeonggaeyeongyotang extract treatment-related changes on the clinical signs and mortalities, the Food consumptions, the Body weights and gains were demonstrated in all dosed levels tested in this study except for 500ml/kg-dosing male group in which a significant(p<0.05) increase of body gains was detected during day 0-7 after dosing. 2. No Hyeonggaeyeongyotang extract treatment-related changes on the pre-coital intervals, the estrus cycles, the mating index, conception rate and fertility index were demonstrated in all dosed levels tested in this study. 3. No Hyeonggaeyeongyotang extract treatment-related gross findings on reproductive organs, the weights of reproductive organs, histopathological findings on reproductive organs, the corpora lutea number, implantation site number, live fetus number, number of resorpted embryo and pre-and post-implatation loss were demonstrated in all dosed levels tested in this study. Conclusions : Base on the results, it is considered that the NOAEL (No-Observed-Adverse-Effect Level) for fertility and early embryonic development toxicity of Hyeonggaeyeongyotang extract was under 2000ml/kg/day in Wistar male and female rats because there no treatment-related changes on the fertility and early embryonic developmental index were demonstrated in all dosed levels tested.
This thesis was designed to find out whether the cadmium content of hair in living animals reflects the status of cadmium accumulation in internal organs or muscles so that this status can be used as a diagnostic method. Forty-five rats were divided into 4 experimental groups and one control group. The control group received a basal diet which contained zinc $100{\mu}g/g$, iron $80{\mu}g/g$ and copper $135{\mu}g/g$. The experimental group received experimental diets sllpplemented with 1, 10, 100 or $1,000{\mu}g/g$ cadmium as cadmium sulfate. Rats were dissected on the 28th or 56th day of experimental periods and tissues, blood and hair samples were taken, dried and burned to ash and analysed. The cadmium, iron zinc and copper concentrations were measured with an atomic absorption spectrophotometer. In addition feed efficiency and hematological changes were observed. The results obtained can be summerized as follows: A marked decrease in feed intake, weight gain and feed efficiency were observed from 1 or 2 weeks of experimental periods, which was in accordance with the dosage and periods. The cadmium contents of kidney, liver, spleen and muscle were significantly increased in all experimental rats; the accumulation was marked in kidney and liver tissues. It was shown that the cadmium contents of hair reflects the cadmium accumulation in internal organs and muscle; the higher the cadmium levels of diet and of rat tissues, the higher the cadmium content of hair. In the $100{\mu}g/g$ group of rats erythrocyte counts and. hemoglobin concentrations were decreased. A significant(p<0.01, p<0.05) increase in iron contents of kidney, liver and muscle was observed in 10, 100, $1,000{\mu}g/g$ groups of rats on the 28th day of experiment. A significant (p<0.01, p<0.05) increase in zinc contents of kidney, liver and muscle was observed in all experimental rats. On the other hand, serum zinc concentration was decreased. A significant(p<0.01) increase in copper contents in the liver was observed on the 28th day in $100{\mu}g/g$ and $1,000{\mu}g/g$ groups of rats. From these results it may be concluded that the analysis of hair for cadmium is a useful diagnostic approach for the cadmium status of internal organs and muscle in living animals.
Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.
This study was undertaken to investigate the effects of Gyoaesamultang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Gyoaesamultang at dose of 5mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately, live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weight of Gyoaesamultang treated group has a tendency to increase compared to that of control group. There were no significant difference in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But Gyoaesamultang administered group showed lower early resorption rate than the control group. Neonatal body weight and number of fetus of Gyoaesamultang group were increased to that of control group. The fetuses of dams treated with Gyoaesamultang didn't showed external malformation. Vertebral and sternal variations were observed in Gyoaesamultang group but, compared to the control, those variations were insignificant. The number of ribs, cervical, thoracic, and lumber were normal. The number of sacral and caudal vertebrae were increased. Fetuses treated with Gyoaesamultang showed significant difference in the number of caudal vertebra(P<0.01). From these results, it can be concluded that Gyoaesamultang showed no toxicity effects on maternal body weight, early resorption rate, and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. Although skeletal variations were showed in vertebrate and sternum, Gyoaesamultang were shown insignificant changes in bone malformation.
The experiments were undertaken to evaluate the effects of herbal medicine, Bojungiggitang and Gwibitang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Bojungiggitang and Gwibitang at dose of 5ml/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and the internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weights of Bojungiggitang and Gwibitang treated group has a tendency to increase compared to that of control group. There were no significant differences in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation and live fetuses. But Bojungiggitang and Gwibitang administered group showed higher implantation rate than the control group. Also, Bojungiggitang and Gwibitang administered groups showed lower early resorption rate than the control group. And Gwibitang had the higher value in all the other groups in all items. From the sex ratio, the number of females were larger than the number of males in the control group, and more males than females in Gwibitang administered group. Neonatal body weight and the number of fetus of Bojungiggitang and Gwibitang group were higher than that of control group. The fetuses of dams treated with Bojungiggitang and Gwibitang did not show external malformation. Vertebral and sternal variations were observed in Bojungiggitang and Gwibitang administered group compared to the control group. Those variations were insignificant. There were no significant changes in number of ribs, cervical, thoracic, lumbar, sacral and caudal vertebras. From these results, it can be concluded that Bojungiggitang and Gwibitang showed no toxic effects on maternal body weight and the number of live fetuses. There were no significant changes in organ weight, hematological data, and reproductive organs. Although skeletal variations were shown in vertebra and sternum, Bojungiggitang, Gwibitang were shown insignificant changes in bone malformation.
The variations of both thiamine and riboflavin value in the organs, viz. liver, small intestine, spleen and kidney of the rats were measured for observing some metabolic changes in the animals during fasting and feeding different quality of diets without V-E supplement. The animal used for the experiment was adult female ablino rat from a pure strain, weighing 225-280g. The animals were divided into 6 groups; the control group, the high carbohydrate diet group, the high carbohydrate diet with V-E group, the high protein diet group, the high protein diet with V-E group, and fasting group. The result obtained are summarized as follows; 1. The thiamine contents in the liver were once increased during early stage of starvation compared with the control group, thereafter they were decreased on the 8 days fasting while the contents in the small intestine and spleen were decreased during 1 to 8 days fasting. 2. The riboflavin contents in the liver and kidney were increased during starvation and the content in the small intestine was no marked change compared with control group. 3. The thiamine contents in the liver and small intestine during feeding the high carbohydrate with V-E supplement diet group were lower than that of the diet without V-E group and the content in the spleen was increased by feeding V-E enriched high carbohydrate diet. 4. The thiamine contents in the liver, small intestine and spleen during feeding the V-E supplemented diets were lower than that of the non-supplemented one's. 5. The riboflavin contents in the liver, small intestine, and kidney were increased during feeding the high carbohydrate diet compared to the control group, and they were decreased during feeding the V-E enriched high carbohydrate diet. 6. The riboflavin contents in each organ were increased during feeding the high protein diet compared to the control group, and they were much increased during 20 to 30 days of feeding the V-E supplemented high protein diet. 7. Therefore, as the above results showed, the variation of thiamine value in the each organs were not markedly changed during feeding different quality of the diets. The thiamine and riboflavin contents in the each organ in the V-E enriched high carbohydrate diet group were lower than without V-E supplemented one's The riboflavin contents in each organ were increased during feeding the high protein diet compared with the control group and the centents were increased during 20 to 30 days of the feeding V-E enriched high protein diet.
Radiolabeled Brazilin(^3H-Brazilin)을 웅성 Wistar Rats에 투여하여 plasma concentration-time profile, urine 및 bile로의 배설, 조직분포 및 plasma protein에 대한 결합률을 살펴보았다. 1. Pharmacokinetic parameters는 다음과 같았다. $t_{1/2}$은 13.7 hr, AUC는 $\53.38\;\mu\textrm{g}{\cdot}hr/ml$, AUMC는 $1013.4\;\mu\textrm{g}{\cdot}hr^2/ml$ MRT는 18.95hr, Vss 17.778l/kg 그리고 CL은 936.77ml/hr.kg였다. 2. Plasma concentration-time profile에서 enterohepaic circulation을 시사하여 2nd peak가 발견되었고. 담즙배설 실험으로 확증할 수가 있었다. 결구투여 후 담즙 배설은 투여량의 64.4%가 10시간에 걸쳐 배설되었고, 3시간째 그 배설속도는 maximum을 이뤘다. 3. Vss는 17.8 l/kg으로 큰 값을 나타냈고, 따라서 뇌를 제외한 대부분의 조직에 Brazilin은 분포하였고 특히 liver와 kidney, epididymus 그리고 testis에 고농도 분포함을 알 수 있었다. 4. 경구투여량의 44.1%가 , 정맥주사 후 투여량의 62.9%가 urine을 통해 배설되었다. Urine을 통해 배설되는 양의 대부분(80%)은 24시간 내에 배설되었다. 5. Plasma protein에 대한 결합율을 한외여과법으로 측정한 결과 $40{\pm}4%$가 결합하는 것으로 나타났다.
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