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Losartan Reduces Remodeling and Apoptosis in an Adriamycin-Induced Cardiomyopathy Rat Model

  • Hyeon A Kim;Kwan Chang Kim;Hyeryon Lee;Young Mi Hong
    • Journal of Chest Surgery
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    • v.56 no.5
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    • pp.295-303
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    • 2023
  • Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

The Effect of Scalp Acupuncture and rTMS on Neuromotor Function in Photothrombotic Stroke Rat Model

  • Jong-Seong Park;Eun-Jong Kim;Min-Keun Song;Jung-Kook Kim;Ganbold Selenge;Sam-Gyu Lee
    • Biomedical Science Letters
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    • v.29 no.4
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    • pp.263-273
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    • 2023
  • This study aimed to investigate effect of scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS) intervention on neuromotor function in photothrombotic cerebral infarction (PCI) rat model. Sixty male SD rats were used. PCI was induced on M1 cortex of right frontal lobe. SA was performed at the Qianding (GV21), Xuanli (GB6) acupoints of ipsilesional M1. Low-frequency rTMS was delivered to contralesional M1. All rats were randomly divided into 4 groups: group A, normal (n, 15); group B, PCI without any stimulation intervention (n, 15); group C, PCI with SA (n, 15); group D, PCI with rTMS (n, 15). Rota-rod test and Ladder rung walking test (LWT) were done weekly for 8 weeks after PCI. SA or rTMS was started from post-PCI 4th day as protocol for 8 weeks. H/E stain and IHC were done. Western blot and qRT-PCR study were performed for MAP2 and BDNF from ipsilesional M1 peri-infarction tissue. Brain MRI study was conducted to quantify the volume of cerebral infarction. As a result, left forelimb and hindlimb function significantly improved more in group C and D than control group, with expressed more BDNF and MAP2. And brain MRI showed focal infarction of right M1 after PCI, and infarction volume progressively decreased in group C and D than group B from post-PCI 5th to 8th week. SA or rTMS was more effective than no intervention group on neuromotor function of PCI rat model. The functional recovery was associated with stimulation intervention-related neurogenesis.

The Analgesic Effect and the Mechanism of Electroacupuncture on Thermal Hyperalgesia in the Rat Model of Collagenase-induced Arthritis: Mediation by Adrenergic Receptors (Collagenase-induced Arthritis Rat Model에서 Thermal Hyperalgesia에 대한 전침(電鍼)의 진통효과(鎭痛效果) 및 기전연구: Adrenergic Mechanism에 대(對)한 연구(硏究))

  • Seo, Byung-Kwan;Park, Dong-Suk;Baek, Yong-Hyeon
    • Journal of Acupuncture Research
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    • v.28 no.2
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    • pp.57-67
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    • 2011
  • 목적 : Collagenase-induced osteoarthritis(OA) 동물 모델에서 전침의 adrenergic mechanism을 연구하고자 한다. 방법 : Collagenase-induced arthritis(CIA)를 유발하기 위하여 5주령의 male Sprague-Dawley rat의 뒷다리 좌측 무릎 관절에 0.05ml의 4mg/ml collagenase solution을 intra-articular 주입하고, 다시 4일 후에 같은 부위에 같은 농도의 collagenase solution을 intra-articular boosting injection 시행한 뒤, gross, histopathological features 및 biomarker activity 변화를 관찰하였다. 예비실험을 통하여 CIA rat model에서 진통효과를 발휘하는 것으로 확인한, 족삼리(足三里) ($ST_{36}$)에 대한 저빈도 train pulse EA stimulation (2Hz, 0.07 mA, 0.3ms)을 침치료 방법으로 적용하였다. 전침의 진통기전을 확인하기 위하여, ${\alpha}1$-adrenergic antagonist (prazosin, 1 mg/kg, i.p.), ${\alpha}2$-adrenergic receptor antagonist (yohimbine, 2mg/kg, i.p.), ${\alpha}1$-adrenergic receptor agonist(phenylephrine, 2mg/kg, i.p.), ${\alpha}2$-adrenergic receptor agonist(clonidine, $40{\mu}g$/kg, i.p.)을 전침시행 20분 전에 복강 내로 전처치하였다. Tail flick unit(Ugo Basile Model 7360)을 이용하여 열자극에 대한 통증역치를 측정하였다. 결과 : 퇴행성관절염 징후(gross, histopathological features)와 통증역치의 변화가 최대값을 나타내는 CIA 유발 4주차에 저빈도 전침자극(train pulse, 2Hz, 0.07mA, 0.3ms)을 족삼리($ST_{36}$)에 적용하였으며, 족삼리 전침의 진통효과는 ${\alpha}2$-adrenergic receptor antagonist(yohimbine, 2mg/kg, i.p.)전처치에 의해 억제되었으나, ${\alpha}1$-adrenergic antagonist(prazosin, 1 mg/kg, i.p.)전처치에는 억제되지 않았다. 또 ${\alpha}2$-adrenergic receptor agonist(clonidine, $40{\mu}g$/kg, i.p.)의 전처치를 통하여 유의한 synergistic analgesic effect가 관찰되었으나, ${\alpha}1$-adrenergic receptor agonist(phenylephrine, 2mg/kg, i.p.)의 전처치는 전침의 진통효과에 synergistic effect를 미치지 않는 것으로 나타났다. 결론 : 저빈도 족삼리 전침은 CIA로 유발된 염증성 통증에 대하여 진통효과를 발휘하며, 이는 ${\alpha}2$-adrenergic receptor에 의하여 매개되는 것으로 보이며 ${\alpha}1$-adrenergic receptor는 영향을 미치지 않는 것으로 사료된다.

A Computational Model of Cytosolic and Mitochondrial [$Ca^{2+}$] in Paced Rat Ventricular Myocytes

  • Youm, Jae-Boum;Choi, Seong-Woo;Jang, Chang-Han;Kim, Hyoung-Kyu;Leem, Chae-Hun;Kim, Na-Ri;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.4
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    • pp.217-239
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    • 2011
  • We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial $Ca^{2+}$ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [$Ca^{2+}]$ bigger in mitochondria as well as in cytosol. As L-type $Ca^{2+}$ channel has key influence on the amplitude of $Ca^{2+}$ -induced $Ca^{2+}$ release, the relation between stimulus frequency and the amplitude of $Ca^{2+}$ transients was examined under the low density (1/10 of control) of L-type $Ca^{2+}$ channel in model simulation, where the relation was reversed. In experiment, block of $Ca^{2+}$ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial $Ca^{2+}$ transients, while it failed to affect the cytosolic $Ca^{2+}$ transients. In computer simulation, the amplitude of cytosolic $Ca^{2+}$ transients was not affected by removal of $Ca^{2+}$ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [$Ca^{2+}$] in cytosol and eventually abolished the $Ca^{2+}$ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type $Ca^{2+}$ channel to total transsarcolemmal $Ca^{2+}$ flux could determine whether the cytosolic $Ca^{2+}$ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic $Ca^{2+}$ affects mitochondrial $Ca^{2+}$ in a beat-to-beat manner, however, removal of $Ca^{2+}$ influx mechanism into mitochondria does not affect the amplitude of cytosolic $Ca^{2+}$ transients.

Beneficial Effects of Herbal Mixture (JAUN-1) on 0.1% Iodoacetamide-induced Gastritis Rat Model (0.1% Iodoacetamide에 의해 유도된 흰쥐 위염 모델에서 한약처방(JAUN-1)의 유익한 효능규명)

  • Han, Kyung-Ju;Koo, Sung-Tae;Hwang, Hye-Suk;Kim, Yu-Sung;Lee, Ji-Eun;Ko, Mi-Mi;Jung, Bong-Yeon;Choi, Sun-Mi
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.6
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    • pp.1549-1554
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    • 2007
  • To verify the effects of JAUN-1, which is a water-extracted herbal mixture, on gastroenteric disorders induced by 0.1 percent of iodoacetamide (IA) in rats. We divided four groups, $Na{\"{\i}}ve$ + Distilled Water (DW), 0.1% IA + DW, 0.1% IA + Proton pump inhibitor (Lansoprazole, 5 mg/kg) and 0.1% IA + Herbal mixture (JAUN-1, 50mg/kg) and performed following experimental methods to confirm its advantageous effects against ulcerogenic stomach in rats induced by 0.1% IA; cell cytotoxicity, analysis of lesions score, Hematoxylin & Eosin (H&E) stain, RT-PCR for ${\beta}-actin$, COX-1 and COX-2 and evaluation of intestinal prokinetic activity. No cytotoxicity was elucidated at the concentration of 1, 5, 10, 50, 100, $500\;{\mu}g/ml$ and 1mg/ml JAUN-1 through MTT Assay using by human stomach epithelial AGS cells, respectively. In addition, the JAUN-1 treated group and the lansoprazole treated group significantly decreased in lesions score compared to the DW treated group in the gastritis induced rat model, and results of immunohistochemistry by H&E staining showed that histological recovery in Proton Pump Inhibitor (PPI) and JAUN-1 treated groups rather than the DW administrated group. Another outcome was that ${\beta}-actin$ relative COX-2 expression level was significantly promoted in the DW treated group while ${\beta}-actin$ relative COX-1 expression level was no meaningful change in this rat model. Finally, intestinal prokinetic activity was recovered from low level of prokinetic activity due to 0.1% IA induced gastritis to the similar level of Normal group. These results suggested that JAUN-1 may have beneficial effects against 0.1% IA-induced gastritis rat model through decreasing lesions score, histological recovery, ${\beta}-actin$ relative COX-1, 2 expression level and prokinetic activity.

The Effects of Bojungikgi-tang on Streptozotocin-induced Diabetic Gastroparesis Rat Model (보중익기탕(補中益氣湯)이 streptozotocin 유발 당뇨병성 위부전마비 백서에 미치는 영향)

  • Kang, Yun-Mi;Kim, Hyo-Jung;Park, Yun-Beom;Jeong, Chan-Mun;Ham, Seong-Ho;Yang, Woong-Mo;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.34 no.6
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    • pp.45-55
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    • 2019
  • Objective : Diabetic gastroparesis is a complication that is defined as delayed gastric emptying and upper gastrointestinal symptoms and often occurs in long-standing diabetic patients. Bojungikgi-tang (BJT) is a traditional oriental herbal formula that has long been used for the treatment of digestive disorders. The purpose of this study was to investigate the effects of BJT on streptozotocin (STZ)-induced diabetic gastroparesis rat model. Methods : Sprague-Dawley (SD) male rats (250-270g) were divided into 13 groups including normal group, STZ-induced diabetic control group, BJT diet (7 various concentrations), and insulin-, glibenclamide-, metformin-treated group were used for the experiments for the comparison. Diabetic gastroparesis was induced by intraperitoneal injection of STZ. The water intake, food intake, body weights and fasting blood glucose levels were measured. After 4 weeks the animals were sacrificed and gastrin, leptin, insulin, hemoglobin A1C (HbA1c), lactate, lactate dehydrogenase (LDH), bilirubin, creatinine, albumin and lipid levels were evaluated. Results : Intraperitoneal injection of BJT for 4 weeks resulted in increased levels of gastrin in blood and decreased leptin and lactate concentration in STZ-induced diabetic gastroparesis rat model. BJT did not affect insulin, fasting glucose, HbA1c, and lipid levels in STZ-induced diabetic gastroparesis rat model. Conclusion : These results indicated that BJT would have protect effect on diabetic gastroparesis through the improvement effect of gastric motility and fatigue syndrome in STZ-induced diabetic rats. This study shows that BJT might be effective for treatment of diabetes and its complications such as gastroparesis.

Attenuated Cerebral Ischemic Injury by Polyethylene Glycol-Conjugated Hemoglobin

  • Cho, Geum-Sil;Choi, In-Young;Choi, Yoo-Keum;Kim, Seul-Ki;Cai, Ying;Nho, Kwang;Lee, Jae-Chul
    • Biomolecules & Therapeutics
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    • v.17 no.3
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    • pp.270-275
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    • 2009
  • Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.

Bone Mineral Density Changes after Ovariectomy in Rats as an Osteopenic Model : Stepwise Description of Double Dorso-Lateral Approach

  • Park, Sung-Bae;Lee, Yoon-Jin;Chung, Chun-Kee
    • Journal of Korean Neurosurgical Society
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    • v.48 no.4
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    • pp.309-312
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    • 2010
  • Objective : This study describes a method for inducing osteopenia using bilateral ovariectomy (OVX), which causes significant changes in bone mineral density (BMD) in rats. Methods : Twenty-five 10-week-old female Sprague Dawley rats were used. Five rats were euthanized after two weeks, and BMD was measured in their femora. The other 20 rats were assigned to one of two groups : a sham group (n = 10), which underwent a sham operation, and an OVX group (n = 10), which underwent bilateral OVX at 12 weeks of age. After six weeks, five rats from each group were euthanized, and BMD was measured in their femora. The same procedures were performed in the remaining rats form each group eight weeks later. Results : The femur BMD was significantly lower in the six-week OVX group than in the six-week sham group, and in the eight-week OVX group than in the eight-week sham group. Conclusion : Bilateral OVX is a safe method for creating an osteopenic rat model. The significant decrease in BMD appears six weeks after bilateral OVX.

Effect of Bee Venom Therapy in a Rat Femoral Artery Model induced Vasospasm (봉독약침(蜂毒藥鍼)이 백서(白鼠) 대퇴동맥(大腿動脈)의 혈관연축(血管攣縮)에 미치는 영향(影響))

  • Kim, Jae-soo;Kim, Hyung-hwan;Choi, Ho-young;Kim, Chang-hwan
    • Journal of Acupuncture Research
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    • v.20 no.1
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    • pp.35-50
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    • 2003
  • In order to study the effect of Bee venom(BV) on the subarachnoid hemorrhage animal model, the autologous whole blood was applied to the vicinity of the sprague dawley rat right femoral artery. Following periarterial application of autologous whole blood(PAB) and intraperitoneal injection of BV(1:5,000 nd 1:500), the vasomotor responses to BV(from 1:500,000 to 1:500) were identified and the histological changes, neovascularized blood vessel were observed. We have shown that alterations in vasomotor and histological findings are elicited following application of periarterial blood and i.p. injection of BV(1:5,000 and 1:500) induced heavy vasospasm and neovascularization on the subarachnoid hemorrhage like model form peripheral artery.

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Acupuncture analgesia in a rat model of neuropathic pain (Neuropathic pain을 일으킨 쥐에 있어서 침의 진통작용)

  • Lim, Kyu-sang
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.12 no.1
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    • pp.143-153
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    • 1999
  • Background: The vasoreactivity of cerebral artery is currently the subject of increasing interest Transcranial Doppler The purpose of this study was to investigate the analgesic effect of acupuncture in a model of neuropathic pain produced by segmental spinal nerve injury (SSI) in rats. The left L5 and L6 spinal nerves of Sprague-Dawley rats were tightly ligated, and one week later, manual or electro-acupuncture was applied for 30 minutes to the contralateral hindlimb (right side) while the animal was lightly anesthetized with halothane. The mechanical threshold of the paw for ipsilateral (left side) hind limb flinching was determined prior to and 0.5, 1, 2, 4, and 24 hours after termination of acupuncture. The mechanical threshold for flinching was significantly elevated for about 4 hours after manual acupuncture applied to the BL. 60 (Kunlun) point or electro-acupuncture to the BL. 60 and BL. 40 (Weizhong) points. However, manual acupuncture applied to the ST. 36 (Zusanli) point was not effective. Furthermore, systemic naloxone pretreatment had no effect on the acupuncture induced threshold elevation. These data suggests that acupuncture produces a point specific, naloxone independent analgesia in a rat neuropathic pain model. ※ This paper is supported by a grant from the '1996 Jusan Foundation of Wonkwang university.)

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