• The Korean Journal of Physiology and Pharmacology
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• v.9 no.5
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• pp.275-282
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• 2005

By using differential display, we identified one of the genes encoding the multi-subunit complex protein V-ATPase, c subunit gene (ATP6L), and showed alterations of the gene expression by oxidative stresses. Expression of the ATP6L gene in Neuro-2A cells was increased by the treatment with $H_2O_2$ and incubation in hypoxic chamber, implying that the expression of the ATP6L gene is regulated by oxidative stresses. To examine mechanisms involved in the regulation of the gene expression by oxidative stresses, the transcriptional activity of the rat ATP6L promoter was studied. Transcription initiation site was determined by primer extension analysis and DNA sequencing, and promoter of the rat ATP6L and its deletion clones were constructed in reporter assay vector. Significant changes of the promoter activities in Neuro-2A cells were observed in two regions within the proximal 1 kbp promoter, and one containing a suppressor was in -195 to -220, which contains GC box that is activated by binding of Sp1 protein. The suppression of promoter activity was lost in mutants of the GC box. We confirmed by electrophoretic mobility shift and supershift assays that Sp1 protein specifically binds to the GC box. The promoter activity was not changed by the $H_2O_2$ treatment and incubation in hypoxic chamber, however, $H_2O_2$ increased the stability of ATP6L mRNA. These data suggest that the expression of the ATP6L gene by oxidative stresses is regulated at posttranscriptional level, whereas the GC box is important in basal activities of the promoter.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.79-85
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• 2010

Purpose: Many trials for new therapeutic approaches such as stem cell-based transplantation have been conducted to improve the repair and regeneration of injured cord tissue and to restore functions following spinal cord injury (SCI) in animals and humans. Adipose tissue-derived stromal cells (ATSCs) have multi-lineage potential to differentiate into cells with neuron-like morphology. Most studies of stem cell transplantation therapy after SCI are focused on cellular regeneration and restoration of motor function, but not on unwanted effects after transplantation such as neuropathic pain. This study was focused on whether transplantation of ATSCs could facilitate or attenuate hindpaw pain responses to heat, cold and mechanical stimulation, as well as on improvement of locomotor function in a rat with SCI. Methods: A spinal cord injury rat model was produced using an NYU impactor by dropping a 10 g rod from a height of 25 mm on to the T9 segment. Human ATSCs (hATSCs; approximately $5{\times}10^5$ cells) or DMEM were injected into the perilesional area 9 days after the SCI. After transplantation, hindpaw withdrawal responses to heat, cold and mechanical allodynia were measured over 7 weeks. Motor recovery on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and on the inclined plane test were also evaluated. Results: The present study demonstrated that increased hindpaw withdrawal responses to cold allodynia was observed in both groups after transplantation, but the development of cold-induced allodynia in the hATSC transplantation group was significantly larger than in the control group. The difference between the two groups in locomotor functional improvement after SCI was also significant. Conclusion: Careful consideration not only of optimal functional benefits but also of unintended side effects such as neuropathic pain is necessary before stem cell transplantation therapy after SCI.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.1
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• pp.59-64
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• 1999

Purpose: The aims of this study are to measure the serum levels of fat soluble vitamins (vitamin A and D) from bile duct ligated rats, and to evaluate the effect of oral bile acids administration to facilitate absorption of fat soluble vitamins. Methods: We measured serum ALT, total bilirubin, vitamin A, and vitamin D of Sprague-Dawley rats 1 week before and 4 weeks after experimental bile duct ligation. Rats were consisted with 3 groups. Group 2 had been fed bile acids and group 3 ursodeoxycholic acid after operation for 4 weeks. Multi-vitamin was given to all groups. Results: 1) Base line (mean value before duct ligation): ALT 74.2 IU, total bilirubin 0.26 mg/dL; vitamin D 13.01 ng/mL vitamin A $0.87\;{\mu}g/mL$, total bile acids $25.16\;{\mu}mol/L$. 2) Four weeks after ligation: ALT 100.7 IU, total bilirubin 2.58 mg/dL; vitamin D 7.89 ng/mL vitamin A $1.37{\mu}g/mL$, total bile acids $278.22\;{\mu}mol/L$. 3) 4 weeks after ligation, each group (group 1, group 2 and group 3) showed vitamin D (7.62, 8.10 and 7.99) ng/mL, vitamin A (1.68, 1.06 and 1.33) ${\mu}g/mL$, total bile acids (233.17, 345.80 and 268.57) ${\mu}mol/L$, which were statistically not significant. Conclusion: Serum level of vitamin A is increased after bile duct ligation although vitamin D is decreased. Oral administration of bile acids does not affect the serum levels of vitamin A and D in bile duct ligated rats.

• Korean Journal of Food Science and Technology
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• v.46 no.2
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• pp.249-255
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• 2014

In this study, the products of Acanthopanax senticosus fermentation were derived from the mycelia of 2 mushrooms, Ganoderma lucidum and Phellinus linteus, to determine their safety in Sprague-Dawley rats. Rats were orally administered the water extracts of A. senticosus fermentation products with G. lucidum (FM-5111) or P. linteus (FM-5131) at dose levels of 0.5, 1.0, or 2.0 g/kg for the single-dose toxicity test and 0.25, 0.5, or 1.0 g/kg for the repeated-dose toxicity test. There were no significant differences in body weight gain, feed intake, or water consumption between control and FM-5111- or FM-5131-treated rats. Hematological and blood biochemistry analysis revealed that none of the investigated parameters were affected by the A. senticosus fermentation products, and no remarkable lesions were observed upon histopathological analysis. We conclude that the A. senticosus fermentation products obtained from mushroom mycelia are safe for long-term administration and could be considered as multi-functional nutrients for the improvement of liver function and immunity.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.377-381
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• 2014

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high $K^+$ solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; $3{\mu}mol/L$); or phenylephrine (Phe; $1{\mu}mol/L$). The relaxation effects of propofol were tested on high $K^+$ or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on $Ca^{2+}$ influx via the L-type $Ca^{2+}$ channels were evaluated by examining contraction-dependent responses to $CaCl_2$ in the absence or presence of propofol (10 to $300{\mu}mol/L$). High $K^+$ solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high $K^+$ solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the $Ca^{2+}$-induced contractions of pulmonary rings exposed to high $K^+$-containing and $Ca^{2+}$-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high $K^+$ solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.4
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• pp.305-312
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• 2015

Paeonol is a major component found in the Paeoniaceae family such as Paeonia suffruticosa Andrews. Paeonia suffruticosa Andrews has traditionally been used to enhance blood flow and relieve joint pain in east Asian countries including China, Korea and Japan. Current research has shown that paeonol blocked the voltage-gated sodium channel and L-type calcium channel. However, there is a lack of research to reveal the relation between cardiac function and blockade of ion channels by paeonol. Therefore, the aim of this study is to investigate whether paeonol has anti-arrhythmic effects via modulating cardiac ion channels. It is collected that the effects of paeonol on multiple ion channels such as the fast sodium channel and L-type calcium channel from published papers. To incorporate the information on multi-channel block, we computed the effects using the mathematical cardiac model of the guinea-pig and rat ventricular cells (Noble 1998 and 1991 model) and induced early after-depolarizations (EADs) to generate an arrhythmia in the whole heart. Paeonol slightly shortened the action potential duration in the normal cardiac ventricular action potential by the inhibition of sodium channel and L-type calcium channel. Paeonol presented the protective effect from EADs by the inactivation of sodium channel but not L-type calcium channel. Paeonol did not show any changes when it treated on normal ventricular cells through the inhibition of sodium channel, but the protective effect of paeonol through sodium channel on EADs was dose-dependent. These findings suggest that paeonol and its original plant may possess anti-arrhythmic activity, which implies their cardioprotective effects.

• Biomedical Science Letters
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• v.16 no.4
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• pp.213-220
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• 2010

Although an adequete intake of calcium (Ca) is recommended for the treatment and prevention of osteoporosis, the intake of Ca should be restricted because of its low rate of intestinal absorption. The purpose of this experiment was to identity the effect of the combined administration of Aquamin F (AQF) (a calcium agent) and lactic acid bacteria (LAB) on osteoporosis. Thirty ovariectomized (OVX) rats and six control rats were assigned to the following six groups, with six animals per group: sham Ca-deficient diet (Ca-D), OVX, LAB, AQF, and LAB-AQF. During the experiment, the body weight was measured; and after the experiment was completed, the serum biochemical analysis, the alkaline phosphatase, calcium, and inorganic phosphorus leves were measured. The tissue of the femur was stained and then scanned via CT. The body weight of the OVX group increased more significantly than that of the control group. The results of the bone mineral content (BMC), Bone mineral density (BMD), serum biochemical analysis and histological test on the femur epiphysis showed no difference between the OVX group and the LAB group, whereas the results of the AQF group were more significant than those of the OVX group. In particular, the LAB+AQF group showed more significant increases in the aforementioned results than the AQF group. This experiment showed that the combined administration of AQF and LAB in ovariectomized rats more significantly increased bone density than did a single administration of either AQF or LAB.

• Natural Product Sciences
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• v.20 no.4
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• pp.251-257
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• 2014

Chungsimyeonja-tang (CSYJT) is an herbal decoction that consists with 12 herbal medicines. CSYJT has been shown to have anti-stress, anti-allergic and anti-oxidant effects. The aim of this study was to determine flavonoid contents in CSYJT and evaluate its protective effect against cisplatin induced nephrotoxicity using both in vitro (porcine renal epithelial cell; PK15 cell) and in vivo (Sprague Dawley rat) experiments. In the present study, thee mean contents of baicalin, wogonoside and baicalein in CSYJT were 14.65, 5.27 and 0.02 mg/g, respectively. The CSYJT extract treatment attenuated the following alteration in porcine renal epithelial (PK15) cell: the increase in reactive oxygen species (ROS), the glutathione depletion and the increase in p53 expression induced by cisplatin treatment. In the in vivo study, rats were orally treated with CSYJT extract once a day for 28 days. Five days before the last treatment, cisplatin (5 mg/kg) was intraperitoneally injected to induce acute renal failure. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels after cisplatin treatment were ameliorated by pretreatment of CSYJT extract. In addition, lipid peroxidation was decreased and antioxidant enzyme (glutathione) was recovered in CSYJT pretreated kidney tissue. In histopathological examination, CSYJT pretreated group showed ameliorated pathological alteration after cisplatin injection with decreased apoptosis. Taken together, pretreatment of CSYJT could ameliorate cisplatin-induced nephrotoxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.451-458
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• 2011

The medicinal mushroom Inonotus obliquus is a traditional and widely used multi-functional fungus. In this study, we have investigated whether Inonotus obliquus (Chaga mushroom) extracts exerts anti-oxidant effects on cisplatin-induced cytotoxicity in auditory cell line, HEI-OC1 cells. First of all, Chaga extracts has no harmful effects on viability of HEI-OC1 cells in the dose range of $65{\sim}125{\mu}g/m{\ell}$. Moreover, it shows cyto-protective effects on the cells treated with cisplatin-induced cytotoxicity in HEI-OC1 cells and the damage of hair cells arrays of the rat primary organ of Corti explants in the presence of cisplatin. Pretreatment with Chaga extracts inhibited the cell death, reactive oxygen species generation (ROS), lipid peroxidation induced by cisplatin. These effects were associated with the induction of antioxidant enzyme by Chaga extracts. We further investigated the effects of Chaga extracts on expression of antioxidant enzymes such as Cu, Zn superoxide dismutase (SOD 1) and Mn SOD (SOD 2) by RT-PCR. In addition, Chaga extracts shows SOD activity and SOD protein expression in cisplatin treated group induced similar to control group. Taken together, these results indicate that Chaga extracts can prevent cisplatin-induced cytotoxicity by radical-scavenging activity (SOD activity) in HEI-OC1 cells. It might be an effective as antioxidant and further studies on the chemo-preventive mechanisms of Inonotus obliquus are needed.

• Journal of Society of Preventive Korean Medicine
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• v.9 no.1
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• pp.119-133
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• 2005

Traditional herbal medicine is widely used among the Korean people, and other eastern Asian countries employ similar therapies as well. In recent years, due to increasing interest in herbal medicines, many researches have been made on the toxicity and side effects of herbal medications. Through private and public media, there have been many opinions suggesting taking herbal medicines is very harmful, especially on the liver and kidney functions. This assertion has been mainly presented by the doctors that practice western medicine, But this assertion is never based on adequate knowledge of herbal medicine. This study aims to provide the evidences that taking herbal medicines is safe on the renal functions. Four frequently used herbal medications(Sipjeondaebotang, Bojungigitang, Ojeoksan, and Yukmijihwangtang) were used to test the toxicity of herbal medicine oh the lab animal model(SD-Rat). There is no significant difference in body weight and kidney weight after herbal medication for 1 month. In all experimental groups, no abnormal findings were observed in histological study, and lab renal function index(BUN, creatinine, uric acid). These results say that four herbal multi-used-medicines, when medicated, is safe from the renal toxicity in lab animal model.