• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.155-162
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• 1999

This study was performed to assess that clinco-therapeutic effect of natural Italian honeybee (Apis mellifera) venom in adjuvant-induced arthritic rat. Ninety Sprague- Dawley rats of male were injected with complete Freund's adjuvant (CFA). Adjuvant arthritis was produced by a single subcutaneous injection of 1 mg Mycobacterium butyricum suspended in 0.1 ml paraffin oil into the right hindpaw. Righting reflex was uniformly lost and considered to be the point of arthritis development on day 14 after CFA injection. Experimental groups were divided into three groups. When arthritis was developed in the rat hind-paw, tested groups were administrated with prednisolone (10 mg/kg, p.o) and honeybee venom (one bee, s.c) at an interval of two days. Control group was subcutaneously injected with 0.1 ml of physiological saline solution in the rat at an interval of two days. Clinical findings, hematological values and histopathological findings were observed during or after the drugs administration. In tested groups, the development of inflammatory edema and polyarthritis on day 14 after treatment was suppressed. No significant differences of hindpaw edema volume and lameness score between prednisolone and honeybee venom groups were observed during or after therapeutic drugs treatment. WBC counts of prednisolone and honeybee venom treatment groups as compared with the control group were getting remarkably decreased during or after the therapeutic drugs administration(p＜0.01). Erosions of articular cartilage and inflammatory cell infiltrations during or after the therapeutic drugs treatment was effectively suppressed in natural honey venom.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.21 no.2
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• pp.203-220
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• 1991

The purpose of this study was to investigate the changes of morphology and structure of bone tissue, caused by administration of high-dose hydrocortisone, elcatonin and cyclophosphamide. In order to carry out experiment, 60 four-week old Sprague-Dawley strain rats weighing about 107 gms were selected and divided into experimental group and control group. The experimental group was subdivided into three groups, assigned fifteen rats for each group, by the different drugs administered. Each experimental group was then categorized as follows: hydrocortisone 30㎎/㎏ b.w. with daily subcutaneous injection, elcatonin 20U/㎏ b.w. with daily subcutaneous injection, and cyclophosphamide 100㎎/㎏ b.w. with a single intraperitoneal injection. Fifteen rats were injected daily with 5㎖/㎏ b.w. of normal saline solution subcutaneously in control group. Rats in control group and experimental group were serially sacrificed on the 6th, the 15th and the 22nd day after injection of normal saline, hydrocortisone, elcatonin and cyclophosphamide, respectively. Being sacrificed, both sides of mandibular condyles were removed and fixed with 10% neutral formaline. The one side of mandibular condyles was radiographed with soft X-ray apparatus. Thereafter, the obtained radiographs were observed, and the bone density of condylar head and condylar neck regions was measured by use of transferring video-based digital radiograph. The other side was further decalcified and embedded in paraffin as usual manner, then sectioned and stained with hematoxylin and eosin, observed by light microscope. The obtained results were as follows: 1. Sclerotic changes with regularly increased trabecular pattern were seen throughout experimental periods in hydrocortisone group. Increased the number of trabecular pattern with irregularity and periodic striation on the periphery of condylar head region were appeared with lapse of time in elcatonin group. In cyclophosphamide group, irregular trabecular pattern and stippled radiopacities on mandibular condyle were observed with lapse of time. 2. The bone density of condylar head region was increased in hydrocortisone group, decreased in elcatonin group, and tended to be decreased in cyclophosphamide group, compared with that of control group according to the experimental periods. 3. The bone density of condylar neck region tended to be rather increased in hydrocortisone group, elcatonin group and cyclophosphamide group, depending on the experimental periods. 4. In microscopic studies, there were irregular trabecular bonds and osteoblastic activity in hydrocortisone group and elcatonin group throughout experimental periods, degenerative cartilage and trabecular bones in the 6th day and densely calcified trabecular bones in the 22nd day in cyclophosphamide group.

• 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.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.171-178
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• 2000

To evaluate the pharmacokinetic properties and tissue distribution of a newly developed recombinant human erythropoietin (GC-rhEPO), we analyzed the plasma and tissue levels of erythropoietin by an ELISA after intravenous (IV) and subcutaneous (SC) adminstration to the male rats at the doses of 20, 100, 500 or 2,500 unit/kg. After single IV bolus injection of GC-rhEPO, the plasma concentration was rapidly increased and decreased with two phases with half-lives of 13.4 min and 2.94 hours. AUC was increased dose- dependently but plasma half-lives remained constant regardless of GC-rhEPO doses. Following SC administration, the plasma concentration increased slowly with half-life of 9.2 hours and reached peak at 8 hours. Mean residence time and bioavailability were 18.2 hours and 44%, respectively. After single IV dose of 100 unit/kg, tissue GC-rhEPO level was higher in bone marrow and spleen, while the depletion rate was slower in liver and bone marrow, indicating the higher affinity of GC-rhEPO to bone marrow. Taken together, the experimental results indicate that GC-rhEPO contained the typical pharmacokinetic properties and the tissue distribution patterns inherent to human erythropoietin.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.197-201
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• 2002

${\beta}-lonone$ has been reported to induce the cytochrome P45O (P45O) 2B1 in rats. In this study, the effects of ${\beta}-ionone$ and an isomer, ${\alpha}-ionone$, on liver P45O IA and 2B expression in Sprague Dawley rats were investigated . Subcutaneous administration of ${\alpha}-$ and ${\beta}-lonone$ 72 and 48hr prior to sacrificing the animals induced the liver microsomal P45O 1A and 2B proteins. P45O 2Bl induction was associated with the accumulation of its corresponding mRNA. 1 Induction by ${\beta}-lonone$ was much higher than that by ${\alpha}-ionone$-ionone in both the mRNA and protein levels. When the route of administration was compared, P45O 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of ${\alpha}-$ and ${\beta}-lonone$ for 24 h induced P45O 2B1 -selective pentoxyresorufin Odepentylase activity comparably in a dose-dependent manner In addition, ${\alpha}-$ and ${\beta}-lonone$ induced the P45O 1A and 2B proteins. These results suggest that ${\alpha}-$ and ${\beta}-lonone$ might be potent P45O 2Bl inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.

• 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 Animal Reproduction
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• v.8 no.1
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• pp.16-21
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• 1984

This experiment was carried out to compare with the nonsurgical and surgical recovery of fertilized eggs in super-ovulated rabbits. Sixty-four eggs recovered were transferred to twelve synchronized, pseudopregnant rabbits to test the viability of the eggs by surgical transfer. Each group(I, II, III) received a single subcutaneous injection of 5mg PGF2${\alpha}$/kg B.W. at 24(Group I), 48(Group II) and 72 hours (Group III) after mating, respectivity. After the administration of PGF2${\alpha}$, vaginal washings were conducted at 3, 6, 9, 12 and 24 hrs, and frequency of vaginal washing was 5 times for the each group (I, II, III). In Group (IV, V, Ⅵ), the rabbits were killed to recover the fertilized eggs from the genital tract at 24(Group Ⅵ), 48(Group V) and 72 hours (Group Ⅵ) after mating, respectively. The results obtained were as follows: 1. Of the total eggs, 69.3%, 73.4% and 66.9% were recovered for Group I, II and III, respectively from the vagina within 6 hrs after PGF2${\alpha}$ injection and particularly for Group III. 2. The rates of egg recovery versus the number of corpora lutea were 55 (51.6-60%), 35.8 (24-52.6%), 33.4 (25-47%) and 72 (70.7-73.0)%, 60.3 (50-71.4)%, 449(44.4-45.5)% in Group I, II, III and Group IV, V, Ⅵ, respectively. 3. Most of eggs recovered were one-cell stage in Group Iand Group IV. More than one half of the eggs recovered in Group II and V were over eight-cell stage, and most of the eggs were so in Group III and Ⅵ. 4. When sixty-four eggs recovered between 24 to 72 hours after mating were transferred to pseudopregnant rabbits. Three recipients were pregnant, and the rate of pregnancy was 25%.

• The Korean Journal of Zoology
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• v.11 no.2
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• pp.48-54
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• 1968

Male rats of the Albino strain received methylene blue in the dose of 40mg/kg by subcutaneous injection and were subjected to total body X-irradiation, 300 roentgen, at 30 minutes after the injection. The protective effect of methylene blue against the single total body X-irradiation was studied for 24 days after X-irradiation with regard to the levels of liver glycogen, blood glucose, and electrolytes in serum. 1. Total body X-irradiation generally casued an increase in the levels of the liver glycogen and blood glucose in both methylene blue treated and control group during the entire experiment. 2. Methylene blue has been shown to delay slightly the increase of the levels of the liver glycogen and blood glucose when comparing with both groups which were given methylene blue and control saline injection before irradiation in the rats. 3. The delay in the increase in the levels of liver glycogen, in experimental group injected with methylene blue, significantly came in two phases. The first phase appeared at there days after the exposure, the second followed at eighth day. It appeared that the recovery phase was at nineteenth day. 4. During the experimental days the levels of the blood glucose increased generally, methylene blue, however, caused delay in two phases; the first at fifth day, the second at eighteenth day after the exposure to X-rays. 5. In electrolytes, there was not a significant difference. The levels of chloride were, however, slightly decreased in both groups, levels of potassium appeared different in two phases at first day and twelfth day, and the levels of sodium appeared to show irregular changes at the same levels, but there was no significant difference. 6. It may be considered that methylene blue greatly reduces the sensitivity of rats to X-rays, provided that methylene blue is given before the exposure.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.100-105
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• 1997

DW-166HC ($^{166}$Holmium-chitosan) is a complex of $^{166}$Ho, $\beta$- and $\gamma$-ray emitter, and chitosan, a polymer of glucosamine, with radiotherapeutic potential. The current study was performed to determine the acute toxicities of $^{165}$Ho-chitosan in mice by two different routes of administration. The both sex mice were given a single intravenous bolus injection of $^{165}$Ho-chitosan complex at doses of 12, 10, 6, 5 and 4 mg/kg or subcutaneous administration at doses of 600, 500, 400 and 300 mg/kg. Chitosan was dosed to control animals as 16 and 800 mg/kg, intravenously and subcutaneously, respectively. The doses of $_{165}$Ho-chitosan complex were expressed as $_{165}$holmium nitrate pentahydrate and the ratio of $^{165}$Ho$(NO_3)_3$).$5H_2O$ to chitosan was 3/4 Severe convulsion and respiratory failure were followed by death within 10 min after intravenous dosing. Transient unilateral hindlimb hypokinesias were found in two mice of 5 mg/kg dosing group during the study period. No abnormalities were observed during the necropsy of survived animals in intravenous dosing group. Only one male animal was found dead in 500 mg/kg subcutaneously dosed group. Alopecia with or without cutaneous ulcer were found in most mice including control animals. During necropsy, omental adhesion was observed in all dose ranges and enlarged spleen was found in several animals including control group. It is suggested that the acute intravenous >).$LD_{50}s$ for male and female mice were 4.90 and 6.03 mg/kg, respectively. The lowest lethal dose in male was 500 mg/kg by subcutaneous administration.

• Toxicological Research
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• v.32 no.3
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• pp.251-258
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• 2016

Mesenchymal stem cells (MSCs) have been identified in multiple types of tissue and exhibit characteristic self-renewal and multi-lineage differentiation abilities. However, the possibility of oncogenic transformation after transplantation is concerning. In this study, we investigated the tumorigenic potential of umbilical cord blood-derived MSCs (hUCB-MSCs) relative to MRC-5 and HeLa cells (negative and positive controls, respectively) both in vitro and in vivo. To evaluate tumorigenicity in vitro, anchorage-independent growth was assessed using the soft agar colony formation assay. hUCB-MSCs and MRC-5 cells formed few colonies, while HeLa cells formed a greater number of larger colonies, indicating that hUCB-MSCs and MRC-5 cells do not have anchorage-independent proliferation potential. To detect tumorigenicity in vivo, hUCB-MSCs were implanted as a single subcutaneous injection into BALB/c-nu mice. No tumor formation was observed in mice transplanted with hUCB-MSCs or MRC-5 cells based on macro- and microscopic examinations; however, all mice transplanted with HeLa cells developed tumors that stained positive for a human gene according to immunohistochemical analysis. In conclusion, hUCB-MSCs do not exhibit tumorigenic potential based on in vitro and in vivo assays under our experimental conditions, providing further evidence of their safety for clinical applications.