• Archives of Pharmacal Research
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• v.14 no.2
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• pp.188-192
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• 1991

Single non-lethal doses of chloroform $(CHCL_3)$ dichlorobromomethane $(CHCL_2Br)$, dibromochloromethane $(CHCIBr_2)$, or bromoform $(CHBr_3)$ were administered to male rats. Routes of exposure including single intraperitional (ip) and subcutaneous (sc) injection were used in order to permit comparison of severity of THM effects and renal toxicity was assessed at varied times following treatment. On an equimolar basis, sc administration of $CHBr_3$ (either 12 or 3 mmoles/kg) is more effective at increasing KW/BW than ip $CHCI_3$ treatment. Plasma urea nitrogen (BUN) following ip THM injections are markedly increased with all four THM at 24 hours post treatment. BUN response to $CHCL_2Br$ and $CHCIBr_3$-effected BUN levels have essentially returned to those of vehicle control. THM sc treatment results in a BUN response similar to that seen following ip treatment, with only the time course being different. With the exception of $CHCL_3$, sc and ip-treatments appear to be equally effective in evoking absolute BUN elevations. These results suggest that THM administration induce renal toxicity dependent upon the route or exposure.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.147-157
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• 2004

Objectives : This experiment was done to evaluate the effects of Hyuntogobon-hwan(HTG) on antioxidant capability and lipidic concentration in blood, both of which are presumed to be related to aging. Methods : 12 week-old SD rats were divided into controlled group, uncontrolled group and HTG group. As controlled and HTG groups were given subcutaneous injection of D-galactose(50mg/kg/rat), at the same time HTG group was administered extract of Hyuntogobon-hwan(270mg/200g). HTG injections continued for 6 weeks. After initial injections, blood was drawn from each group and the following were measured: the activity of SOD, GSH-px, catalase in erythrocytes, TSARS value, concentration of total lipid, tryglyceride in blood plasma. Results : The activities of SOD and GSH-px in erythrocytes increased significantly in HTG group compared with controlled group. The activity of catalase seemed to increase slightly, but it was barely noticeable. The concentration of total lipid in plasma decreased significantly in HTG group compared with controlled group. The value of TBARS in plasma seemed to decrease slightly, but it was barely noticeable. Conclusions : According to the above results, Hyuntogobon-hwan has an influence on aging by virtue of activation of antioxidative enzyme systems in erythrocytes and concentrations of lipid in blood plasma.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.12-18
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• 2002

Silymarin and curcumin have been used for supportive treatment of liver disease of difffrent etiology due to their hepatoprotective activities. The present study was carried out to investigate the hepatoprotective efffcts of silymarin and/or curcuma extract against hepatotoxins induced liver injury. To investigate hepatoprotective effects, the silymarin and/or curcuma extract were pre-treated orally to experimental animals. And thereafter a single dose of hepatotoxin, carbon tetrachloride ($CCl_4$) and acetaminophen were administered through oral or intraperitoneal route, respectively. Chronic liver damage was induced by subcutaneous injection of $CCl_4$ for 3 weeks (2 times/week). Hepatoprotective and therapeutic effects were monitored by estimating serurn ALT and AST levels and by measuring hepatic glutathione (GSH) and malondialdehyde (MDA)levels. Collagen type 1 was detected with irnrnunostaining to assess fibrosis. The results showed that the mix-ture of silymarin and curcuma extract significantly reduced serum biochemistry levels and MDA levels com-pared with those of control group in both acute and chronic animal models. In antifibrotic effect, the relative hepatic collagen content was significantly decreased by silymarin and/or curcuma extract treatment. It was concluded that the complex of silymarin and curcuma extract have a both hepatoprotective and therapeutic effect synergically in rat liver injury induced by heptotoxins.

• Korean Journal of Oriental Medicine
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• v.2 no.1
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• pp.205-225
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• 1996

This study has been carried out to investigate the effects of Youngyanggaksan (YGS) extract on the anticonvulsive, antipyretic, anlgesic, sedative and GABAergic system of experimental animals. The results of this study were as follows : 1. YGS extract prolonged significantly the beginning time to convulsion and time to death induced by strychnine. 2. YGS extract prolonged significantly the time to death induced by electrical shock of ECT unit (3sec, 200F, 25mA). 3. On the experiment of hypothermic effects of YGS extract on the rectal temperature of rats, YGS extract decreased significantly the rectal temperature of rats. 4. On the experiment of antipyretic effects of YGS extract on the febrile induced by the subcutaneous injection of $150{\mu}g/kg$ endotoxin in rats, YGS extract decreased significantly the rectal temperature of rats. 5. On the experiment of analgesic effects of YGS extract on the writhing syndrome induced by intraperitoneal injection 0.7% acetic acid 1ml/100g in rats, the writhing syndrome was reduced significantly by administration of YGS extract. 6. On the experiment of sedative effects of YGS extract on spontaneous motor activity measured by wheel cage method in mice, the spontaneous motor activity was reduced significantly by administration of YGS extract. 7. On the experiment of effects of YGS extract on the activity of GABA-transaminase(GABA-T) in rat brains after 21 days of oral administration of YGS extract, the activity of GABA-T was reduced significantly by administration of YGS extract. 8. On the experiment of effects of YGS extract on the activity concentration of GABA in rat brains after 21 days of oral administration of YGS extract the activity concentration of GABA was reduced significantly by administration of YGS extract. 9. On the experiment of effects of YGS extract on the activity of GAD in rat brains after 21 days of oral adminstration of YGS extract, the activity of GAD was reduced significantly by administration of YGS extract. According to the those results, Youngyanggaksan extract reveals the effects on the anticonvulsive, antipyretic, anlgesic, sedative and GABAergic system.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.3
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• pp.111-122
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• 2009

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to investigate the morphological effects and metallothionein (MT) expression by zinc pretreatment in the course of time of cadmium-induced testicular injury in rat. Fifty male Spraque-Dawley rats weighing 160~180 g were divided into two groups : saline-pretreated cadmium group and zinc-pretreated cadmium group. Rats of two groups received subcutaneous injection of saline and 100 mg/kg $ZnSO_4$ at 0, 2, 5 and 8 hrs intervals respectively. Cadmium chloride (4.5 mg/kg $CdCl_2$) was administrated intraperitoneally at 2 hrs after zinc injection and rats were killed 0, 12, 24, 48 and 72 hrs later. Testicular tissue damages, interstitial (Leydig) cells status and MT expression were determined using hematoxylin-eosin stained sections and a computerized image analysis system on sections immunostained with a mouse anti-metallothionein respectively. Zinc pretreatment was significantly reduced testicular damages in five pathological categories after cadmium administation. The number of surviving interstitial cells was significantly higher in the zinc-pretreated group than in the saline-preatreated group at 48 and 72 hrs after cadmium administration. Non-damaged testis showed the positivity of MT staining in spermatogenic cells, Sertoli cells and endothelium of blood vessel, but not in the Leydig cells. The positivity of MT staining in saline-pretreated group was significantly reduced at 24 hrs after cadmium administration, whereas zinc-pretreated group showed strong MT positive staining similar to the 0 hr by 42 hrs after cadmium administration. In damaged testis, MT positive staining was also observed in the Leydig cells of both groups. These results suggest that a major preventive effect of zinc against cadmium-induced testicular toxicity may be due to its ability to reduce the cytotoxicity of cadmium in spermatogenic cells and Leydig cells by inhibiting the susceptibility of the testis to cadmium but not MT production by cadmium.

• Korean Journal of Clinical Laboratory Science
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• v.42 no.3
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• pp.136-148
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• 2010

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to investigate the morphological effects and metallothionein (MT) expression by zinc pretreatment in the course of time of cadmium-induced testicular injury in rat. Fifty male Spraque-Dawley rats weighing 160-180 g were divided into two groups: saline-pretreated cadmium group and zinc-pretreated cadmium group. Rats of two groups received subcutaneous injection of saline and 100 mg/kg $ZnSO_4$ at 0, 2, 5 and 8 hrs intervals respectively. Cadmium chloride (4.5 mg/kg $CdCl_2$) was administrated intraperitoneally at 2 hr after zinc injection and rats were killed 0, 12, 24, 48 and 72 hrs later. Testicular tissue damages, Interstitial (Leydig) cells status and MT expression were determined using hematoxylin-eosin stained sections and a computerized image analysis system on sections immunostained with a mouse anti-metallothionein respectively. Zinc pretreatment was significantly reduced testicular damages in five pathological categories after cadmium administation. The number of surviving interstitial cells was significantly higher in the zinc-pretreated group than in the saline-preatreated group at 48 and 72 hrs after cadmium administration. Non-damaged testis showed the positivity of MT staining in spermatogenic cells, Sertoli cells and endothelium of blood vessel, but not in the Leydig cells. The potitivity of MT staining in saline-pretreated group was significantly reduced at 24 hrs after cadmium administration, whereas zinc-pretreated group showed strong MT positive staining similar to the 0 hr by 42 hrs after cadmium administration. In damaged testis, MT positive staining was also observed in the Leydig cells of both groups. These results suggest a major preventive effect of zinc against cadmium-induced testiculat toxicity may be due to its ability to reduce the cytotoxicity of cadmium in spermatogenic cells and Leydig cells by inhibiting the susceptibility of the testis to cadmium but not MT production by cadmium.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.182-190
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• 2006

Objective : Based on immunological mechanisms, this study examined whether subcutaneous (s.c.) injection of Clematis mandshurica Maxim. water extract (CMA) has anti-inflammatory effects, and its effect on $TNF-{\alpha}$, IL-1 and IL-10 release from synoviocytes on adjuvant arthritis (AA) in the rat. Methods : Complete Freund's adjuvant was used to induce AA in rats. Synoviocytes were separated by the method of collagenase and DNase digestion Synoviocytes proliferation was assayed by 3-(4, 5 dimethylthiazol 2 yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. $TNF-{\alpha}$, IL-1 and interleukin-10 (IL-10) production of synoviocytes was measured with ELISA. The expression of IL-10 mRNA of synoviocytes was determined using RT PCR. Results : There were significant secondary inflammatory reactions in AA rats, accompanied by the decrease of body and immune organs weight simultaneously. Synoviocytes proliferation of AA rats significantly increased, and the levels of $TNF-{\alpha}$ and IL-1 in supernatants of synoviocytes in AA rats were also elevated compared with the sham group. The administration of CMA (2, 5, 10 mg/kg, s.c.) reduced the above changes significantly. In contrast to $TNF-{\alpha}$ and IL-1, IL-10 production and the level of its mRNA of synoviocytes in AA rats apparently decreased. CMA (2, 5, 10 mg/kg, s.c.) markedly increased IL-10 in synoviocytes at protein and transcription level. Conclusion : The results indicate that CMA has a beneficial effect on rat AA due to modulating inflammatory cytokine production of synoviocytes, which play a crucial role in the pathogenesis of this disease.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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• pp.61-70
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• 2005

Objective : This study was performed to investigate the effects of OWT on allergic bronchial asthma. Methods : The mice were divided into 4 groups induced the allergic bronchial asthma : Three groups(OWT-1, OWT-2, OWT-3) treated OWT and non-treated group(Control). Three oral administration of the herbal solution of OWT were carried out 1 lime a day for 2 weeks before antigen sensitization. 2 days later, the mice were sensitized with a subcutaneous injection of ovalbumin(OA) and then 13 days later they were provoked with OA aerosols. Then the cell numbers in bronchoalveolar lavage fluid(BALF), serum level of IgE, WBC, RBC and HCB were measured. Results : 1. On the neutrophil in BALF, OWT-1 group is significantly increased compared with the control group. 2. On the eosinophil in BALF, OWT-1 group tends to decrease compared with the control group but insignificant. 3. On the lymphocyte in BALF, OWT-2 group is significantly decreased compared with the control group. 4. On the macrophage in BALF, OWT-2 group is significantly increased compared with the control group. 5. On the serum IgE, groups OWT-1, OWT-2 and OWT-3 are significantly decreased compared with the control group. 6. On WBC in blood, OWT-1 group is significantly decreased compared with the control group. Conclusions : Based on the above results, it is assumed that the oral administration of OWT can help the treatment of allergic bronchial asthma.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.1-10
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• 2003

Background : Asthma is a chronic inflammatory disorder under immunological influence. Gamichunggumgangwha-tang (CG, Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (YM, Jiaweiliuweidihuang-tang) are herbal tonics for asthma from traditional herbal medicine. Objective : To evaluate the effect of CG and YM on immune cell & serum OA-specific IgE in broncho-alveolar lavage fluid (BALF) in a rat asthma model. Materials and Methods : Rats were sensitized with OA; at day I sensitized group and CG and YM groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1 ml of 0.9% saline containing $6{\times}10^9$ B. pertussis bacilli was injected by Lp. 14 days after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2% (wt/vol) OA. A day after local immunization, BALF was collected from the rats. Rats were orally administered with each of CG and YM extract for 14 days since the day after local immunization. Lymphocyte, CD4＋ T cell and CD8＋ T cell counts, CD4＋/CD8＋ ratio in BALF, change of serum OA-specific IgE level, CD4＋ T cell and CD8＋ T cell percentages in the peripheral blood were measured and evaluated. Results : CG and YM showed an alleviating effect on asthmatic responses of rats. CG decreased total cell, lymphocyte, CD4＋ T cells in BALF, and serum OA-specific IgE level as compared with the control group. YM decreased lymphocytes as compared with the control group. CD4＋/CD8＋ ratio in BALF from the CG and YM groups and serum OA-specific IgE level from the YM group didn't show any significant variation from the control group. Conclusion : CG alleviated asthmatic hyperreactivity of the immune system through CD4＋ T cells and serum IgE. Further the study of this immune system modulating mechanism is expected.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.106-110
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• 2007

Background: A phosphodiesterase 5 inhibitor, sildenafil, has been effective against nociception. Several lines of evidence have demonstrated the role of the GABAergic pathway in the modulation of nociception. The impact of the GABA receptors on sildenafil was studied using the formalin test at the spinal level. Methods: Male SD rats were prepared for intrathecal catheterization. The formalin test was induced by subcutaneous injection of formalin solution. The change in the activity of sildenafil was examined after pre-treatment with GABA receptor antagonists ($GABA_A$ receptor antagonist, bicuculline; $GABA_B$ receptor antagonist, saclofen). Results: Intrathecal sildenafil dose-dependently attenuated the flinching observed during phase 1 and 2 in the formalin test. The antinociceptive effect of sildenafil was reversed by the $GABA_B$ receptor antagonist (saclofen) but not by the $GABA_A$ receptor antagonist (bicuculline) in both phases. Conclusions: Intrathecal sildenafil suppressed acute pain and the facilitated pain state. The antinociception of sildenafil is mediated via the $GABA_B$ receptor, but not the $GABA_A$ receptor, at the spinal level.