• Title/Summary/Keyword: model rat

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Inhibitory Effects of Dihydrexidine on Catecholamine Release from the Rat Adrenal Medulla

  • Lee, Jae-Hwang;Lim, Hyo-Jeong;Lim, Dong-Yoon
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.32-42
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    • 2009
  • The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

Ameliorative Effect of Schisandra chinensis and Ribes fasciculatum Extracts on Hydrogen Peroxide-Induced Neuronal Cell Death in Neuroblastic PC12 Cells and the Scopolamine-Induced Cognitive Impairment in a Rat Model (오미자칠해목 추출물의 과산화수소로 유발된 PC12뇌세포 사멸과 스코폴라민으로 유발된 렛드 동물모델에 대한 개선 효과)

  • Park, Eun-kuk;Han, Kyung-Hoon;Heo, Jae-Hyeok;Kim, Nam-Ki;Bae, Mun-Hyoung;Seo, Young-Ha;Yong, Yoon-joong;Jeong, Seon-Yong;Choi, Chun-Whan
    • The Korean Journal of Food And Nutrition
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    • v.33 no.3
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    • pp.347-355
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    • 2020
  • Cognitive impairment is considered to be key research topics in the field of neurodegenerative diseases and in understanding of learning and memory. In the present study, we investigated neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts in hydrogen peroxide-induced neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley® (SD) rat in vivo. Apoptotic cell death in neuroblastic PC12 cell line was induced by hydrogen peroxide for 1 hour at 100 μM. However, mixture of SC and RF treatment prevented peroxide induced PC12 cell death with no neurotoxic effects. For in vivo experiment, the effect of SC and RF extracts on scopolamine-induced cognitive impairment in SD rat was evaluated by spontaneous alternation behavior in Y-Maze test. After 30 min scopolamine injection, the scopolamine-induced rats presented significantly decreased % spontaneous alteration and acetylcholine level, compared to non-induced group. However, treatment of SC+RF extracts rescued the reduced % spontaneous alteration with acetylcholine concentration from hippocampus in scopolamine-induced rats. These results suggested that mixture of SC and RF extract may be a potential natural therapeutic agent for the prevention of cognitive impairment.

Effects of Electroacupuncture on the Expression of Cyclooxygenase in the Spinal Cord of Carrageenan-injected Rat (전침이 carrageenan유발 동통모델의 척수배각내 cyclooxygenase 발현에 미치는 영향)

  • Choi, Yung-Hyun;Lee, Yong-Tae;Choi, Byung-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.749-752
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    • 2005
  • We investigated the effects of electroacupuncture (EA) on the expression of cyclooxygenase in the spinal cord of acute inflammatory pain model. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw of Sprague-Dawley. Bilateral 2 Hz EA stimulation with 0.5 mA, 1 mA and 3 mA were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles in carrageenan-injected rats. Three hours after carrageenan injection, effects of EA on cyclooxygenase (COX) expression were observed in the dorsal horn of the spinal cord using immunohistochemical method. The immunoreaction of COX-1 tended to increase in the superficial laminae and the neck of the dorsal horn as compared with normal. The COX-2 immunoreaction in the carrageenan-injected rat was also significantly increased in the all regions of the dorsal horn as compared with normal one. However, COX-1 immunoreaction in carrageenan-injected rat were decreased in the superficial laminae and neck of the dorsal horn by low intensity of EA stimulation. Except high intensity of EA stimulation in the superficial laminae, COX-2 expression was attenuated in all regions of the dorsal horn by all types of EA treatment. It is concluded that EA treatment may attenuate inflammatory pain in carrageenan-injected rat through modulating expression of COX-2 in the dorsal horn of the spinal cord.

Quantification of Metabolic Alterations of Dorsolateral Pre-Frontal Cortex in Depression SD Rat by MR Spectroscopy

  • Hong, Sung-Tak;Choe, Bo-Young;Choi, Chi-Bong;Park, Cheong-Soo;Hong, Kwan-Soo
    • Journal of the Korean Magnetic Resonance Society
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    • v.10 no.2
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    • pp.126-140
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    • 2006
  • Purpose: Contrary to the human study, it has rarely investigated metabolic alterations in the dorsolateral prefrontal cortex (DLPFC) of depressed rats versus age and sex-matched controls using proton magnetic resonance spectroscopy (MRS). Thus, the purpose of this research was to verify the feasibility of metabolic differences between the normal rat and the depression model rat. Materials and Methods: A homogeneous group of 20 SD male rats was used for MRI and in vivo 1H MRS. To induce a depressed status in SD rats, we performed the forced swimming test (FST). Using image-guide, water suppressed in vivo 1H MRS with 4.7 T MRI/MRS system, NAA/Cr and Cho/Cr ratios were mainly measured between depressed rats and normal subjects. Results: In depressed rats, increased Cho/Cr ratio was measured versus control subjects. However, no significant group effect for NAA/Cr was observed between case-control pairs. Discussion and Conclusions: The present 1H MRS study shows significant brain metabolic alterations of dorsolateral prefrontal cortex with experimental depressed status of SD rat induced by FST compared to normal subjects. This result provides new evidence that in vivo 1 H MRS may be a useful modality for detecting localized functional neurochemical markers alterations in left DLPFC in SD rats.

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Pharmacological effects of Artemisia messes-schmidiana var viridis on 1-naphthylisothiocyanate-induced intrahepatic cholestasis in rat (1-naphthylisothiocyanate에 기인된 랫드의 간내성 담즙분비 정지에 대한 인진호(Artemisia messes-schmidiana var viridis)의 약리학적 효과)

  • Kim, Kil-soo;Lee, Byeong-noh;Park, Joon-hyoung
    • Korean Journal of Veterinary Research
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    • v.35 no.3
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    • pp.481-488
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    • 1995
  • In oriental folk medicine, Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used for more than 20 years as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. Various biochemical and morphological changes including biliary epithelial and parenchymal cell necrosis occur in the liver of animals treated with ANIT. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of secretion volume and total bile acids level in bile juice, and that of serum AST, ALT, ALP, bilirubin, and glucose levels in rat. AMWE stimulated bile secretion and recovered ANIT-induced cholestasis. Bile acid concentrations increased to more than 60% compared with normal by ANIT, which were returned toward normal value with AMWE treatment. Serum AST and ALT activities were increased by ANIT and yet which were significantly decreased with AMWE treatment. In addition, this effect was apparent in AMWE pretreatment group. Serum glucose levels were increased with AMWE and ANIT, while were decreased compared with control in AMWE posttreatment group. Increased serum total bilirubin contents and ALP activities by ANIT were significantly decreased with AMWE posttreatment. In conclusion, AMWE exerted bile acid-independent choleresis effect and then improved to normal conditions ANIT-induced cholestatic syndromes. Also, AMWE have protective and regenerative effect of hepatocytes in rat.

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Metabolic Interactions of Cannabinoids with Steroid Hormones

  • Watanabe, Kazuhito
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.57-64
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    • 2007
  • Metabolic interactions of the three major cannabinoids, ${\Delta}^9$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) with steroid hormones were investigated. These cannabioids concentration-dependently inhibited $3{\beta}$-hydroxysteroid dehydrogenase and $17{\alpha}$-hydroxylase in rat adrenal and testis microsomes. CBD and CBN were the most potent inhibitors of $3{\beta}$-phydroxysteroid dehydrogenase and progesterone $17{\alpha}$-hydroxylase, respectively, in rat testis microsomes. Three cannabinoids highly attenuated hCG-stimulated testosterone production in rat testicular interstitial cells. These cannabinoids also decreased in levels of mRNA and protein of StAR in the rat testis cells. These results indicate that the cannabinoids could interact with steroid hormones, and exert their modulatory effects on endocrine and testicular functions. Metabolic interaction of a THC metabolite, $7{\beta}$-hydroxy-${\Delta}^8$-THC with steroids is also investigated. Monkey liver microsomes catalyzed the stereoselective oxidation of $7{\beta}$-hydroxy-${\Delta}^8$-THC to 7-oxo-${\Delta}^8$-THC, so-called microsomal alcohol oxygenase (MALCO). The reaction is catalyzed by CYP3A8 in the monkey liver microsomes, and required NADH as well as NADPH as an efficient cofactor, and its activity is stimulated by some steroids such as testosterone and progesterone. Kinetic analyses revealed that MALCO-catalyze reaction showed positive cooperativity. In order to explain the metabolic interaction between the cannabinoid metabolite and testosterone, we propose a novel kinetic model involving at least three binding sites for mechanism of the metabolic interactions.

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Forsythiae Fructus Extract Inhibits RANKL-Induced Osteoclast Differentiation and Prevent Bone Loss in OVX-Induced Osteoporosis Rat (연교의 파골세포 분화 및 골 흡수 억제 기전 연구)

  • Eom, Ji-Whan;Kim, Jae-Hyun;Kim, Minsun;Kim, Sangwoo;Shin, Hwajeong;Jung, Hyuk-Sang;Sohn, Youngjoo
    • Korean Journal of Acupuncture
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    • v.36 no.2
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    • pp.115-126
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    • 2019
  • Objectives : Osteoporosis is a condition characterized by low bone mass and increased bone fragility. It has become a major problem of senior citizens. The purpose of this study is to experiment the effect of water extract of Forsythiae Fructus (wFF) on osteoclast differentiation; and the other purpose is to examine the effect of wFF on osteoporosis in ovariectomized rat. Methods : To investigate the effect of wFF on osteoclast differentiation and activity, RAW 264.7 cells were used. The number of TRAP positive cell, TRAP activity, pit area, mRNA expression of makers (RANK, TRAP, CA II, CTK, MMP-9, NFATc1, c-Fos), protein expression of makers (NFATc1, c-Fos) were investigated. For in vivo study, 40 female Sprague-Dawley (SD) rats were induced osteoporosis by ovariectomy (OVX) and then tested for anti-osteoporosis effect by administration of wFF. Results : wFF suppressed osteoclatogenesis, TRAP activity and pit area formation. Moreover, wFF decreased the expression of master differentiation factors (NFATc1, c-Fos) and also reduced the osteoclastogenesis-related markers (TRAP, CA II, CTK, MMP-9). These suggest that wFF inhibit osteoclasts differentiation and bone resorption. In the OVX rat model, wFF inhibited decreasing of BMD and trabecular area. Conclusions : Forsythiae Fructus should be effective for osteoporosis prevention and treatment.

Inhibitory effects of abietic acid in testosterone-induced benign prostatic hyperplastic rats (송진 유래 abietic acid가 전립선 비대증 모델 rat에 미치는 영향)

  • So-Young, Kim;Yoo-Jin, Kim;Yong-ung, Kim;Mi Ryeo, Kim
    • The Korea Journal of Herbology
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    • v.38 no.2
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    • pp.27-34
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    • 2023
  • Objectives : Currently, the benign prostatic hyperplasia (BPH) is one of the most common urogenital disorder in old men. We were performed to determine the effects of abietic acid (AC), component of pine resin, in benign prostatic hyperplastic Sprague-Dawley rat (SD rat) induced by testosterone injection (IP). Methods : We monitored body weights in SD rat at start and end date of experiment. After end of experiment, the prostate weights were measured in SD rats. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels was performed in serum. And we determined the 5-alpha reductase Ⅱ activity, testosterone levels, and dihydrotestosterone levels in prostate tissue and serum using ELISA kit. Results : As results, the prostate wights were increased in BPH group compared to normal group and were decreased in fina, AC30, and AC 50 groups, respectively. Serum GOT levels were decreased in AC50 group compared to BPH group. And Serum GPT levels of AC30 and AC50 groups were lower than BPH group. In addition, the 5-alpha reductase Ⅱ activity, testosterone levels, and dihydrotestosterone levels were decreased the fina, AC10, AC30, and AC 50 groups contrast to the BPH group. Furthermore, 5-alpha reductase Ⅱ activity, testosterone levels, and dihydrotestosterone levels were decreased dose dependent in AC groups compared to BPH group. Conclusion : These results suggest that AC could be used as a potential material for the treatment of BPH by decreasing the androgen levels in benign prostatic hyperplasia model rats.

Introduction of Visceral Pain Model to Test of Visceral Nociception in the Rats (백서의 내장 신경통 연구를 위한 Visceral Pain Model(VPM)의 소개)

  • Lee, Chul-Woo
    • The Korean Journal of Pain
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    • v.8 no.1
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    • pp.25-30
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    • 1995
  • Anlgesic agents against visceral pain typically rely on a noxious chemical irritation of the peritoneum, e. g., acetic acid and phenylquinone writhing test. While useful, this type of assay depends upon an acute inflammation and the release of local alogens. Further, ethical and scientific constraints prevent repeated assessments in a single animal, thereby compounding the difficulty of assessing tolerance development to analgesic agents. To overcome these constraints, Colburn et al. developed a model for mechanical visceral pain model (VPM) based on a repeatable and reversible duodenal distention in the rat. A chronic indwelling intraduodenal balloon catheter is well tolerated and upon inflation produces a writhing response graded in proportion to distention. This response is inhibited by morphine in a dose dependent manner. We found that a model for visceral pain was thought to be a great value.

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Studies on the Wound Healing by the PVA-soft hydrogel (화상 및 창상 치료용 외용제제 개발에 대한 기초 연구)

  • 조동현;신영희
    • YAKHAK HOEJI
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    • v.48 no.1
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    • pp.55-59
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    • 2004
  • A PVA-soft hydrogel, which is a semi-solid form in container, whereas after applying on the skin, it formed a thin layer within a few minutes. In this study, we prepared a novel type PVA-soft hydrogel containing 6-methyluracil as active drug, and the therapeutic value was characterized. To evaluate the therapeutic value of the PVA-soft hydrogel containing drug, various animal models, thermal burn model, incision & excision wound rat model were used. We also measured the wound size and breaking strength to calculate the wound healing extent after single or multiple administration. The wound size of soft hydrogel treated group decreased rapidly than that of control group after multiple dosing in excision wound model. And, the breaking strength of the soft hydrogel treated group was greater than that of control group in incision wound model.