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The effects of estradiol and its metabolites on the regulation of CYP1A1 expression.

  • Euno, Joung-Ki;Yhong, Sheen-Yhun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2002.10a
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    • pp.170-170
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    • 2002
  • College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

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Anti-Obesity and Hypolipidemic Effects of Dietary Levan in High Fat Diet-Induced Obese Rats

  • Kang, Soon-Ah;Hong, Kyung-Hee;Jang, Ki-Hyo;Kim, So-Hye;Lee, Kyung-Hee;Chang, Byung-Il;Kim, Chul-Ho;Choue, Ryo-Won
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.796-804
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    • 2004
  • We found previously that dietary high fat caused obesity, and levan supplementation to the regular diet reduced adiposity and serum lipids. In the present study, we examined the effects of levan [high-molecular-mass $\beta$-(2,6)-linked fructose polymer] supplement on the development of obesity and lipid metabolism in rats fed with high-fat diet. Thus, to determine whether the dietary levan may have the anti-obesity and hypolipidemic effects, 4-wk-old Sprague Dawley male rats were fed with high-fat diet for 6 wk to induce obesity, and subsequently fed with 0, 1, 5, or 10% levan supplemented high-fat diets (w/w) for another 4 wk. For the comparison, a normal control group was fed with AIN-76A diet. Supplementation with levan resulted in a significant reduction of high-fat-induced body weight gain, white fat (i.e., epididymal, visceral, and peritoneal fat) development, adipocyte hypertrophy, and the development of hyperinsulinemia and hyperlipidemia in a dose-dependent manner. Serum triglyceride and free fatty acid levels were greatly reduced by levan supplementation. Serum total cholesterol level was reduced, whereas the HDL cholesterol level was increased by dietary levan. The expression of uncoupling protein (UCP) was increased by dietary high fat, and was further induced by levan supplementation. The mRNA level of UCP1, 2, and 3 in brown adipose tissue (BAT) and UCP3 in skeletal muscle was upregulated in rats fed with dietary levan. In conclusion, upregulated UCP mRNA expression may contribute to suppression of development of obesity through increased energy expenditure. The present results suggest that levan supplementation to the diet is beneficial in suppressing diet-induced obesity and hyperlipidemia.

Expression of Tight Junction Molecule In The Human Serum-Induced Aggregation of Human Abdominal Adipose-Derived Stem Cells In Vitro

  • Yoon, A Young;Yun, Sujin;Yang, HyeJin;Lim, Yoon Hwa;Kim, Haekwon
    • Development and Reproduction
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    • v.18 no.4
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    • pp.213-224
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    • 2014
  • Previously we have shown that human abdominal adipose derived-stem cells (ADSCs) could aggregate during the high-density culture in the presence of human serum (HS). In the present study, we observed that human cord blood serum (CBS) and follicular fluid (HFF) also induced aggregation. Similarly, porcine serum could induce aggregation whereas bovine and sheep sera induced little aggregation. qRT-PCR analyses demonstrated that, compared to FBS-cultured ADSCs, HS-cultured cells exhibited higher level of mRNA expression of CLDN3, -6, -7, -15, and -16 genes among the tight junction proteins. ADSCs examined at the time of aggregation by culture with HS, BSA, HFF, CBS, or porcine serum showed significantly higher level of mRNA expression of JAM2 among JAM family members. In contrast, cells cultured in FBS, bovine serum or sheep serum, showed lower level of JAM2 expression. Immunocytochemical analyses demonstrated that the aggregates of HS-cultured cells (HS-Agg) showed intense staining against the anti-JAM2 antibody whereas neither non-aggregated cells (HS-Ex) nor FBS-cultured cells exhibited weak staining. Western blot results showed that HS-Agg expressed JAM2 protein more prominently than HS-Ex and FBS-cultured cells, both of latter reveled weaker intensity. These results suggest that the aggregation property of ADSCs during high-density culture would be dependent on the specific components of serum, and that JAM2 molecule could play a role in the animal sera-induced aggregation in vitro.

Vasoactive Intestinal Peptide (VIP)-induced Enzyme Secretion in Rat Pancreatic Tissue is not associated with Activation of Nitric Oxide Synthase(NOS) and Increase in Cyclic GMP Level

  • Nam, Tae-Kyun;Han, Jeung-Whan;Nam, Suk-Woo;Seo, Dong-Wan;Lee, Young-Jin;Ko, Young-Kwon;Lee, Hyang-Woo
    • Archives of Pharmacal Research
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    • v.19 no.3
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    • pp.201-206
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    • 1996
  • Nitric oxide (NO) is thought to be a second messenger involved in secretion. Upon stimulating pancreatic acinar cells with cholecystokinin-pancreozymin (CCK-PZ), NO formation has been shown to be associated with increased levels of cGMP (Seo et al., 1995). To elucidate the signaling pathway of VIP-induced enzyme secretion, we investigated the NO and cGMP synthesis steps as potential steps where two signal pathways triggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by treatment with VIP has no relationship with NOS activity and cGMP level. This conclusion was derived from the following findings that VIP treatment of rat pancreatic tissue increased amylase release as well as protein output in a dose- and time-dependent manner, whereas NOS activity and cGMP synthesis were not affected by VIP treatment as monitored by NOS activity assay and determining cGMP level, which was further confirmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases enzyme secretion in rat pancreatic tissue, but the two hormones are different in their mode of action. Together the results suggest that signaling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-induced pathway.

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Studies on the Physiological Activities of Caragana chamlagu Roots -Effects on the Hyperlipemia, Hyperglycemia and Liver Damage- (골담초근의 생리활성 -고지질, 고혈당 및 간손상에 미치는 영향-)

  • Kim, Hak-Sun;Kim, Il-Hyuk
    • Korean Journal of Pharmacognosy
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    • v.23 no.2
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    • pp.96-105
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    • 1992
  • The studies were attempted to evaluated the therapeutic effects of various fractions(ether, methanol, butanol) of Caragana chamlagu roots on the hyperlipemia induced by feeding the diet containing 1%, cholesterol and 0.5%, cholic acid in rats, and on the hyperglycemia induced by streptozotocin in rats. Also the preventive effects of these fractions were studies on the liver damage in $CCl_4-intoxicated$ rats. The followings were obtained as the results: 1.The butanol fraction was significantly shown to down the serum lipid level in 1%, cholesterol and 0.5%, cholic acid diet-feeding rats and streptozotocin-induced hyperglycemic rats. Cholesterol level in $CCl_4-intoxicated$ rats was reduced in the case of all pre-treated groups. 2.The serum glucose level of streptozotocin-induced hyperglycemic rats was significantly decreased by the administration of various fractions of C. chamlagu roots, and the lipid-peroxidation of pancreas was significantly decreased in the case of administration of these fractions. 3.The activates of s-GOT and s-GPT were decreased by the administration of various fractions, especially in butanol fraction, of C. chamlagu roots in the $CCl_4-intoxicated$ rats. The liver lipid-peroxidation was decreased by administration of 200mg/kg of these fractions in the $CCl_4-intoxicated$ rats. In histological observation, hepatic cellular necrosis and fatty acid deposit were increased remarkably by $CCl_4-intoxication$, but the pretreatment of various fractions of C. chamlagu roots improved the pathological change of parenchymatous cell necrosis and fatty change around centrilobular area of the control.

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Protective effects of Artemisia arborescens essential oil on oestroprogestative treatment induced hepatotoxicity

  • Dhibi, Sabah;Ettaya, Amani;Elfeki, Abdelfettah;Hfaiedh, Najla
    • Nutrition Research and Practice
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    • v.9 no.5
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    • pp.466-471
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    • 2015
  • BACKGROUND: Currently, natural products have been shown to exhibit interesting biological and pharmacological activities and are used as chemotherapeutic agents. The purpose of this study, conducted on Wistar rats, was to evaluate the beneficial effects of Artemisia arborescens oil on oestroprogestative treatment induced damage on liver. MATERIALS/METHODS: A total of 36 Wistar rats were divided into 4 groups; a control group (n = 9), a group of rats who received oestroprogestative treatment by intraperitoneal injection (n = 9), a group pre-treated with Artemisia arborescens then injected with oestroprogestative treatment (n = 9), and a group pre-treated with Artemisia arborescens (n = 9). To minimize the handling stress, animals from each group were sacrificed rapidly by decapitation. Blood serum was obtained by centrifugation and the livers were removed, cleaned of fat, and stored at $-80^{\circ}C$ until use. RESULTS: In the current study, oestroprogestative poisoning resulted in oxidative stress, which was demonstrated by 1) a significant increase of lipid peroxidation level in hepatic tissue 2) increased levels of serum transaminases (aspartate amino transferase and serum alanine amino transferase), alkaline phosphatase, glycemia and triglycerides and a decrease in the level of cholesterol 3) alteration of hepatic architecture. Pre-administration of Artemisia arborescens oil was found to alleviate oestroprogestative treatment induced damage by lowering lipid peroxidation level and by increasing activity of catalase, superoxide-dismutase, and glutathione-peroxidase in liver and by reducing disruption of biochemical parameters. CONCLUSION: Therefore, the results obtained in this study confirmed that Artemisia essential oil protects against oestroprogestative administration induced hepatotoxicity by restoration of liver activities.

Benzyl Isothiocyanate-Induced Cytotoxicity via the Inhibition of Autophagy and Lysosomal Function in AGS Cells

  • Po, Wah Wah;Choi, Won Seok;Khing, Tin Myo;Lee, Ji-Yun;Lee, Jong Hyuk;Bang, Joon Seok;Min, Young Sil;Jeong, Ji Hoon;Sohn, Uy Dong
    • Biomolecules & Therapeutics
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    • v.30 no.4
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    • pp.348-359
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    • 2022
  • Gastric adenocarcinoma is among the top causes of cancer-related death and is one of the most commonly diagnosed carcinomas worldwide. Benzyl isothiocyanate (BITC) has been reported to inhibit the gastric cancer metastasis. In our previous study, BITC induced apoptosis in AGS cells. The purpose of the present study was to investigate the effect of BITC on autophagy mechanism in AGS cells. First, the AGS cells were treated with 5, 10, or 15 μM BITC for 24 h, followed by an analysis of the autophagy mechanism. The expression level of autophagy proteins involved in different steps of autophagy, such as LC3B, p62/SQSTM1, Atg5-Atg12, Beclin1, p-mTOR/mTOR ratio, and class III PI3K was measured in the BITC-treated cells. Lysosomal function was investigated using cathepsin activity and Bafilomycin A1, an autophagy degradation stage inhibitor. Methods including qPCR, western blotting, and immunocytochemistry were employed to detect the protein expression levels. Acridine orange staining and omnicathepsin assay were conducted to analyze the lysosomal function. siRNA transfection was performed to knock down the LC3B gene. BITC reduced the level of autophagy protein such as Beclin 1, class III PI3K, and Atg5-Atg12. BITC also induced lysosomal dysfunction which was shown as reducing cathepsin activity, protein level of cathepsin, and enlargement of acidic vesicle. Overall, the results showed that the BITC-induced AGS cell death mechanism also comprises the inhibition of the cytoprotective autophagy at both initiation and degradation steps.

Numerical Analysis of Flow-Induced Noise in Suction Nozzle of a Vacuum Cleaner with a Rotary Fan (팬이 장착된 진공청소기 흡입 노즐내 유로 유동 소음해석)

  • Park, I-Sun;Lee, Sung-Cheol;Oh, Jang-Keun;Sohn, Chae-Hoon
    • Proceedings of the Korean Society for Noise and Vibration Engineering Conference
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    • 2006.11a
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    • pp.208-211
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    • 2006
  • Flow resistance induced by each element in suction nozzle of a vacuum cleaner with a rotary fan is investigated numerically and its relation with flow-induced noise is examined. Flow resistance and vorticity in suction nozzle are calculated and it is found that they are closely related with flow-induced noise. From numerical results, it is suggested that reduction of flow resistance effectively increases all-suction performance and decreases sound pressure level of noise generated in the suction nozzle.

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Inhibitory effects of Maduryung(Aristolochiae Fructus) on alcohol, acetaminophen and galactosamine induced hepatitis in rats (마두령(馬兜鈴)의 흰쥐 간염(肝炎) 억제(抑制) 효과(效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Park Ho-Hwan;Jeong Gyu-Mahn
    • The Journal of Pediatrics of Korean Medicine
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    • v.9 no.1
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    • pp.237-256
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    • 1995
  • Maduryung Extract, one of herbal medicine was tested for inhibitory effect to alcohol, acetaminophen and d-galactosamine induced hepatitis in rats. The results were as follows. 1. Increaced serum GOT, GPT levels by alcohol were significantly decreased by Maduryung extract.(p<0.01) 2. Maduryung extract decreaced GOT value in acetaminophen induced hepatitis and this effect may be due to increace of GSH level in liver tissue.(p<0.05) 3. Repeat administration of Maduryung extract showed inhibitory effect on s-GOT, s-GPT levels in d-galactosamine induced hepatitis. (p<0.05) According to the above results, it seems that Maduryung could be use as drug for alcohol or drug induced hepatitis treatment.

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Antithrombotic Effect of Galla Rhois (오배자의 항혈전 효과)

  • Song, Gyu-Yong;Park, Byung-Jun;Kim, Sung-Hoon
    • Korean Journal of Pharmacognosy
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    • v.33 no.2 s.129
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    • pp.120-123
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    • 2002
  • The possibility of Galla Rhois(GR) water extract as an antithrombotic agent was investigated. The effect of GR on platelet aggregation in human platelet-rich plasma(PRP) induced by collagen and ADP in vitro and coagulation parameters in a pathological model induced by endotoxin and hydrocortisone acetate(HA) in vivo were examined. In platelet aggregation assay, GR extract significantly inhibited platelet aggregation induced by collagen and ADP in a dose-dependent manner. GR extract significantly increased the number of platelet and shortened prothrombin time(PT) and activated thromboplastin time(APTT) as compared with the control in pathological model induced by endotoxin and HA. Also, GR extract significantly increased fibrinogen level as compared with the control in a pathological model induced HA. These results suggest that GR may be a promising antithrombotic agent.