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Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

  • Lee, Heaji;Lim, Yunsook
    • Nutrition Research and Practice
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    • v.13 no.5
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    • pp.377-383
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    • 2019
  • BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ${\geq}250mg/dL$), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear $factor-{\kappa}B$ pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Antioxidant effect of Lonicera Caerulea on heat stress-treated male mice

  • Kang, Donghun;Kim, Daeyoung
    • Journal of Animal Reproduction and Biotechnology
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    • v.36 no.4
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    • pp.220-229
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    • 2021
  • Lonicera caerulea (Honey berry, HB) has been used in medical treatment in Russia, Japan, China and Korea. It has high level of vitamin C and polyphenolics. Polyphenolics can improve anti-inflammatory effect and prevent cancer, diabetes mellitus type 2. Also, Vitamin C is a representative anti-oxidant. however, it is still unknown what effect it will have on the oxidation stress of the reproductive system. In previous studies, ROS can be produced when it is exposed to heat stress and has negative effect on sperm's maturation, capacitation, hyperactivation, acrosome reaction and fusion of egg and sperm. Therefore, the purpose of this study is to investigate the antioxidant effects of L. Caerulea on the sperm and mice. At first, it conducted using ICR mouse (n = 20) for 4 weeks. There are four groups of mice (n = 5 per group). Also, L. Caerulea was taken by oral gavage. Group I (control) kept at 23℃-27℃ and administer D.W (0.5 mL/day), Likewise, Group II (HB) kept at room temperature but gave HB (250 mg/kg, 0.5 mL/day), Group III (HB + HS) received heat stress (40℃) using hyperthermia induction chamber and gave HB at same dose. and Group IV (HS) exposed heat stress only. Mainly, we showed degree of gene expression using Western blot in SOD, HSP 70, 17β-HSD and Real-time PCR. It can find correlation between intracellular activity like steroid hormone, apoptosis under ROS and antioxidant activity of L. Caerulea.

A Review of Rat Models of Avascular Necrosis of the Femoral Head Treated with Natural Extracts

  • Go-Woon, Kim;Hyoung-Yong, Park;Yeon-Cheol, Park
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.239-248
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    • 2022
  • To determine the effect of Korean medicine treatment of avascular necrosis of the femoral head (ANFH) this study reviewed both single ingredients and bioactive compounds in the treatment of ANFH in a rat model. Literature was retrieved from PubMed and Google Scholar using the keywords "femur head necrosis," "natural extract," and "rat." The data from studies analyzed included: rats' characteristics, development methods of ANFH, natural extracts administration, observation methods, and outcome indicators. Two independent researchers screened all articles retrieved and 26 studies were chosen. The most used rat species was the Sprague Dawley rat (76.9%). To induce ANFH, steroid injections (46.2%), and oral gavage (53.8%) were typically used. Studies focused mainly on factors affecting bone formation (65.3%), and apoptosis (53.8%). Research on ANFH focused on using traditional natural substances mentioned in classical literature to confirm its effectiveness against anti-inflammation, osteogenesis, and cell death. ANFH has a diverse etiology, therefore research models such as genetic analysis of human-derived samples from ANFH patients may shed more light on the condition. Moreover, research into herbal medicines and pharmacoacupuncture treatment of ANFH should precede.

The Impairment of Thyroid Hormones Homeostasis after Short-Term Exposure to Di(2-ethylhexyl)phthalate in Adolescent Male Rats

  • Kim, Sang-Yon;Hong, Yeon-Pyo;Yang, Yun-Jung
    • Development and Reproduction
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    • v.25 no.4
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    • pp.293-298
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    • 2021
  • Di(2-ethylhexyl)phthalate (DEHP) could induce metabolic disorders through interfering with thyroid homeostasis. Therefore, we evaluated the effects of short term to environmental relevant doses of DEHP on thyroid hormones. Four week old Sprague-Dawley (SD) rats were treated with vehicle (corn oil), and DEHP 0.75, 7.5, and 150 mg/kg/day. The rats were treated with once daily by oral gavage and were sacrificed with after 1 week. They were measured body weight and relative thyroid weight, serum thyroid hormones and histological changes of thyroid. There was no difference in body weight between the control and DEHP exposed rats. Relative thyroid weight in DEHP 150 mg/kg/day treated group was significantly lower than control. Serum thyroxine levels was decreased in rats exposed to 0.75 and 150 mg/kg/day DEHP. No histological changes were observed in the thyroid of rats administered DEHP compared to control. Exposure to DEHP at environmental relevant levels, even short-term exposure, can cause hypothyroidism in adolescent rats even the exposure period is relative short.

Acute toxicity study of 77 herbal formulas according to GLP guidelines in rats (흰쥐에서 GLP 기준에 의한 한약처방 77종의 단회 투여 급성 독성 연구)

  • Hyeun-kyoo Shin;Woo-Young Jeon;Chang-Seob Seo;Mee-Young Lee
    • The Journal of Korean Medicine
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    • v.44 no.3
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    • pp.29-38
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    • 2023
  • Objectives: This study aimed to investigate the acute oral toxicity of 77 herbal formulas and performed in male and female Sprague-Dawley (SD) rats as per the guidelines mentioned in Ministry of Food and Drug Safety. Methods: Each sex of SD rat were administered a single dose (2000 or 5000 mg/kg) of 77 herbal formulas via oral gavage; the control group received vehicle only. After administration, the mortality, clinical signs, gross findings, and body weight were followed up for 15 days. Results: After administration of 77 herbal formulas, mortality, clinical signs, body weight changes, and gross findings related to the test substances were not observed in both male and female groups. Conclusion: Our results demonstrate the single-dose oral administration of 77 herbal formulas produced no mortality indicating the approximate lethal dose is greater than 2000 or 5000 mg/kg body weight.

Morphological, ultrastructural, and biochemical changes induced by sodium fluoride in the tongue of adult male albino rat and the ameliorative effect of resveratrol

  • Emtethal M. El-Bestawy;Asmaa M. Tolba;Walaa A. Rashad
    • Anatomy and Cell Biology
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    • v.55 no.4
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    • pp.483-496
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    • 2022
  • Little knowledge is available about the effects of fluoride exposure on the tongue. This study evaluated the effects of sodium fluoride (NaF) on the tongue ultrastructure and detected the ameliorative effects of resveratrol. Forty adult albino rats were separated into 4 groups: the control group was given a balanced diet and purified water. The NaF treated group: received 10 mg/kg/d dissolved in 2.5 ml distilled water once daily for 30 days orally. The NaF+resveratrol group: received NaF 10 mg/kg/d orally together with resveratrol in a dose of 30 mg/kg daily for 30 days. The resveratrol group was subjected to resveratrol in a dose of 30 mg/kg/d by oral gavage for 30 days. Sections were stained with hematoxylin & eosin, and Masson's trichrome. Tumor necrosis factor α immunohistochemical study and electron microscopic examinations were done. The oxidative stress markers malondialdehyde, antioxidant reduced glutathione, and the total antioxidant capacity were measured. The NaF group revealed ulceration, necrotic muscle fibers, distorted papillae and a significant increase in malondialdehyde level, and a significant decrease in glutathione and the total antioxidant levels. In the NaF+resveratrol group, pathological changes were less, and the oxidant levels were decreased by the administration of resveratrol with NaF. In conclusion, NaF adversely affects the ultrastructure of the adult rat tongue and resveratrol can ameliorate this effect.

Antidepressant-like Effects of Schisandra chinensis Baillon Water Extract on Animal Model Induced by Chronic Mild Stress (만성스트레스로 유발된 우울증 동물모델에서 오미자 물 추출물의 항우울 효과)

  • Kang, Min Gu;Kim, Young Hwa;Im, A Rang;Nam, Byung Soo;Chae, Sung Wook;Lee, Mi Young
    • Korean Journal of Medicinal Crop Science
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    • v.22 no.3
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    • pp.196-202
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    • 2014
  • Depression is one of the most common neuropsychiatric disorders and has been associated with the neuroendocrine system and alterations in behavior. Schisandra chinensis Baillon is one of major medicinal plants used as a Korea medicine and food sources, and has been processed in the fields of various food products and medicinal herbs. The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviors in laboratory mice or rat. The CMS procedure induced some behavioral changes that are compatible with the common expectations, i.e. 'anhedonic' behavior and can affect corticosterone level. The present study, Schisandra chinensis extract administration by daily gavage from the 3 weeks exhibited an antidepressant-like effect on CMS-induced depression in mice. Schisandra chinensis extract administration at dose of 200mg/kg significantly increased the sucrose consumption, and decreased the immobility durations in forced swim test and tail suspension test. Furthermore the corticosterone level decreased than control group. In conclusion, Schisandra chinensis extract showed antidepressant-like effects on sucrose preference test, forced swimming test and tail suspension test based on CMS model.

A 4-week Repeated Oral Dose Toxicity Study of Plant Sterol Esters in Sprague-Dawley Rats

  • Kim, Jong-Choon;Yang, Byung-Chul;Lim, Kwang-Hyeon;Kang, Boo-Hyon;Kim, Choong-Yong;Kim, Kab-Sik;Chung, Dae-Won;Chung, Moon-Koo
    • Toxicological Research
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    • v.18 no.1
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    • pp.31-41
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    • 2002
  • The present study was conducted to investigate the potential subacute toxicity of plant sterol esters by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to rats at dose levels of 0, 1000, 3000, and 9000 mg/kg/day for 4 weeks. During the test period, clinical sign, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. A reduction in the body weight was observed in females of the 9000 mg/kg group on day 27 after the initiation of treatment, but not in males of the group. There were no treatment-related effects on mortality, clinical sign, food and water consumption, ophthalmoscopy, urinarlysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. Based on these results, it was concluded that the 4-week repeated oral dose of plant sterol esters resulted in suppressed body weight in female rats at a dose level of 9000 mg/kg/day. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 9000 mg/kg/day for males and 5000 mg/kg/day for females.

28-day Repeated-dose Toxicity Study of Flutamide, an Anti- androgenic Agent, in Rats: Establishment of Screening Methods for Endocrine Disruptors (내분비계 장애물질 검색법의 확립을 위한 항안드로젠성 물질 flutamide의 랫드 28일 반복투여 독성실험)

  • 정문구;김종춘;임광현;하창수
    • Toxicological Research
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    • v.16 no.2
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    • pp.163-172
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    • 2000
  • Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.

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A Study on Acute Oral Toxicity of Pyungwi-san and Fermented Pyungwi-san in ICR Mice (ICR 마우스를 이용한 평위산과 발효평위산 급성독성 연구)

  • Jang, Doo-Rye;Hwang, Youn-Hwan;Jung, Ki-Youn;Ha, Jeong-Ho;Park, Hwa-Yong;Ma, Jin-Yeul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.1
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    • pp.59-68
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    • 2013
  • Objectives: This study was conducted to investigate the acute toxicity of Pyungwi-san(Pingwei-san in Chinese) in ICR mice, according to KFDA and OECD guideline. Methods: In the present study, 15 male and female ICR mice administrated singly by gavage at dose levels of 0 and 2000 mg/kg of Pyungwi-san. During the experimental period, no treatment-related death was observed. There were no adverse effects on clinical signs, body weight, and gross findings at all treatment groups. Results: These results showed that the single oral adminstration of Pyungwi-san (Pingwei-san) did not cause any toxic effect at the dose levels of 2000 mg/kg in rats. Conclusions: Taken together, the median lethal dose($LD_{50}$) of Pyungwi-san (Pingwei-san) was considered to be over 2000 mg/kg body for both sexes.