• Journal of fish pathology
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• v.18 no.1
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• pp.59-66
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• 2005

In the present paper, the immunostimulatory effects of Korean mistletoe (Viscum album Coloratum) on the non-specific immune responses of Japanese eel (Anguilla japonica) were examined. Eel were innoculated with mistletoe, Freund's complete adjuvant (FCA), or phosphate-buffered saline (PBS) as a control into their peritoneal cavities. The number of nitrobule tetrazolium (NBT)-positive cells in the head kidney of fish was significantly increased by the second day post-injection of mistletoe. ROI products were more enhanced in mistletoe-injected fish kidney leucocytes than in FCA-injected ones. The level of lysozyme activity detected in the serum of fish 2 days after injection with mistletoe was also significantly higher than that found in the serum of the control fish. The appropriate concentration of mistletoe to induce the highest level of serum lysozyme activity was revealed to 1000${\mu}g$/200 g of fish. In phagocytic activity assay, mistletoe-sensitized eel kidney phagocytes captured more zymosan than did the control fish. Korean mistletoe appeared to be a good activator of the non-specific immune responses of Japanese eel.

• Toxicological Research
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• v.14 no.3
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• pp.307-313
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• 1998

Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.

• Korean Journal of Pharmacognosy
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• v.46 no.3
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• pp.203-207
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• 2015

This study was performed to examine the antigenic potential of purified bee venom (Apis mellifera L., PBV) collected using bee venom collector. Antigenic potential of PBV was examined by active systemic anaphylaxis (ASA) in guinea pigs. PBV was subcutaneously administered at 0.025 and 0.05 mg/kg and also as a suspension with adjuvant (Freund's complete adjuvant, FCA). Ovalbumin (OVA) as a suspension with adjuvant was used to introduce positive control response. In the weight measurement and clinical observation, experimental groups didn't show any significant changes compared with control group. In the autopsy of body, the abnormalities of lung were detected only in the positive control. In the ASA test, experimental groups didn't show any symptoms of anaphylaxis like piloerection, hyperpnea and staggering gait. These results suggested that PBV didn't have antigenic potential in guinea pig.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.48-52
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• 1997

The antigenic potential of CFA-001, cefazolin, a cephalosporin derivative produced by an enzy-matic semisynthesis, was determined in Hartley guinea pigs. A battery of tests employed consisted of active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA), and indirect hemagglutination test (IHA). The results were as follows: 1) In ASA, no signs attributable to anaphylaxis was observed in guinea pigs sensitized with CFA-001, whereas OVA-sensitized animals induced severe anaphylactic symptoms; 2) guinea pigs did not produce antibodies against CFA-001 when sensitized with or without Freund's complete adjuvant (FCA) in homologous PCA tests. Meanwhile, antibodies against ovalbumin (OVA) were clearly detected; 3) No CFA-001-specific hemagglutination was observed in the IHA using sera obtained from CFA-001- sensitized guinea pigs. These results suggest that CFA-001 has no antigenicity potential in guinea pigs.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.336-342
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• 2002

MeOH extract of Kochia scoparia was fractionated into $CHCl_3-$, EtOAc- and BuOH extracts and the last fraction were hydrolyzed by 3%-NaOH ($MeOH-H_2O$) to compare the bioactivities on antinociceptive and anti-inflammatory effects. Silica gel column chromatography of BuOH fraction afforded a large amount of $3-Ο-{\beta}-D-xylopyranosyl {\;}(1{\rightarrow}3)-{\beta}-D-glucuronopyranosyl$ oleanolic acid (momordin Ic, 4) and that of acid hydrolysate of BuOH fraction gave $3-Ο-{\beta}-D-glucuronopyranosyl oleanolic$ acid (momordin Ib, 3), its 6'-Ο-methyl ester (2) and oleanolic acid (1). Silica gel column chromatography of alkaline hydrolysate afforded a large amount of 4. MeOH extract and both EtOAc- and BuOH fractions were active in the rheumatoidal rat induced Freund's complete adjuvant reagent (FCA) whereas $CHCl_3$ fraction was inactive. Compound 1 and 4 showed significant activities in the same assay but oleanolic acid 3-Ο-glucuronopyranoside (3) showed no activity. These fashions were also observed in carrageenan-induced edema of the rat and in the antinociceptive activity tests undertaken in hot plate- and writhing methods. These results suggest that momordin Ic and its aglycone, oleanolic acid, could be active principles for rheumatoid arthritis.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.117-124
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• 1997

The analgesic effects of DA-5018, a new caosaucin derivative, were evaluated in various experimental pain models. Drugs were administered subcutaneously or topically. When drugs were administered subcutaneously, 1) the $ED_{50}$ of DA-5018, morphine . HCI, capsaicin and acetaminophen were 0.091-2.0, 0.3-4.3, 1.4-26.5 and 45.4-643 mg/kg, respectively in various pain or inflammatory models including acetic acid writhing, formalin, tail flick, Randall-Selitto, hot plate and crouton oil-induced ear edema test, 2) the AD2 values (the dose for doubling of pain threshold of vehicle control) of DA-5018, capsaicin and ketoprpgin were 1.07 $\pm$ 0. 18, 23.47$\pm$4.46 and 2.97$\pm$0.43 mg/kg in Freund's complete adjuvant (FCA)-induced arthritic pain model. And by topical application, 1) neither DA-5018 0.3% cream nor Zostrix-HP (capsaicin 0.075%) were effective in formalin test, 2) although DA-5018 0.3% cream significantly inhibited the croton oil-induced ear edema being better than Zostrix-HP and Kenofen (ketoprofen 3%). 3) In FCA model, DA-5018 0.3% cream reversed the decreased pain threshold of arthritic rat from 136.4 g (day 0) to 289.0 g (day 5) and 250.1 g (day 10), which was similar to Zostrix-HP. These results suggest that DA-5018 administered subcutaneously has a potent and broad analgesic spectrum than nonsteroidal antiinflammatory drugs against acute and chronic pain, and by topical application it exerts comparable analgesic and antiinglammaatory effects to capsaicin cream.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.575-585
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• 2000

This study was performed to observe the influence of host immune response on the chemotherapy of mice experimentally infected with Fasciola hepatica. Following immunosuppression with prednisolone or immunoenhancement with Freund's complete adjuvant(FCA), mice were experimentally infected with 3 Fasciola hepatica metacercariae and treated with closantel at 1 week post infection. In the group of mice infected with metacercariae alone, 2 mice of 10 were dead at 10 weeks post infection(20% mortality), and adult flukes were recovered from the liver and the peritoneal cavity of the remaining 8 mice(100% infectivity). In the group of mice treated with prednisolone and infected with metacercariae, 8 of 10 mice died before euthanasia with a mean time of death earlier than the control group (p<0.05). In the group of immunosuppressed mice infected with metacercariae and treated with closantel 20mg/kg, 4 of 10 mice died before sacrifice. In the group of mice infected and treated with closantel 20mg/kg, mortality and infectivity was 10% and 30%, respectively. Similar results were observed in mice infected and treated with closantel 5mg/kg which resulted in 10% and 50% mortality and infectivity, respectively. These results indicated that the efficacy of closantel treatment was decreased in immunosuppressed mice, while the pathogenicity was increased. In immunoenhanced mice infected with metacercariae, on the other hand, the efficacy of chemotherapy with both 5mg/kg or 20mg/kg closantel resulted in only 10% infectivity. The results shown in this study strongly suggest that a close interaction between chemotherapy against F hepatica with closantel and the host immune system exists. Considering that fascioliasis is a zoonosis, treatment regimen against the infection to immunosuppressed patients may require a concurrent prescription of an appro-priate immuno-enhancing adjuvant.

• Journal of Environmental Science International
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• v.26 no.2
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• pp.249-256
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• 2017

In this study, we evaluated the potential of 70% ethanol extract from Persicaria nepalensis (PNE) as a cosmetic ingredient by primary skin irritation, ocular irritation, and maximization tests for delayed hypersensitivity in New Zealand white rabbits and Hartley guinea pig. Skin safety study was performed to evaluate the potential toxicity of PNE using the primary irritation test. In the primary irritation test, 50% PNE was applied to the skin, and no adverse reactions such as erythema and edema were observed at the intact skin sites. Therefore, PNE was classified as a practically non-irritating material based on a primary irritation index of "0.0.". In the ocular irritation test, the 50% PNE applied did not show any adverse reactions in the different parts of rabbit eyes, including the cornea, iris, and conjunctiva. Thus, PNE was classified as a practically non-irritating material based on an acute ocular irritation index of "0.0.". Skin sensitization was tested by the Guinea Pig Maximization Test (GPMT) and Freund's Complete Adjuvant (FCA) using an intradermal injection of 10% PNE. Edema and erythema were not observed 24 and 48 h after the topical application of PNE in skin sensitization test, which exhibited a sensitization score of "0.0.". Therefore, it can be suggested that P. nepalensis could be used as potential candidates for cosmoceutical ingredients, without any major side effects.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.84-84
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• 2001

The heartwood of Rhus verniciflua has been known to be effective for lingering intoxication and diabetes mellitus and rheumatoidal arthritis in traditional folk medicine in Korea. We have previously reported that antimutagenic effect of flavonoids derived from the heartwood extract of R. verniciflua, and sulfuretin was the active component. Recently, we have demonstrated that sulfuretin could be an anti-inflammatory principle of the R. verniciflua heartwood partially dependent on cyclooxigenase-inhibitory activity. The present study was undertaken to demonstrate the anti-rheumatoidal arthritis effect of the R. verniciflua heartwood extract, its EtOAc fraction and the main flavonoids, sulfuretin and fustin. All the test samples showed variably significant inhibitory effects on hind paw edema induced by Freund's complete adjuvant reagent (FCA reagent). Sulfuretin treatment with 10 mg/kg (i.p.) for seven days showed the inhibitory effect of 54.2${\pm}$3.0%, Similar trends in RA- and CRP tests, vascular permeability test and trypsin inhibitor test were also found. In addition, no dead mouse was found even when the dose was increased up to 5,000 mg/kg (i.p.). Treatment with 250-1,500 mg/kg on normal rats did not show any marked toxicological significances in the tests of body weight gain, wet weight of organs and hepatic functions. These results suggested that the heartwood of R. verniciflua could be an adequate crude drug for rheumatoidal arthritis with an active component of sulfuretin. The toxicological safety of the heartwood of R, verniciflua is contrasted to known severe allergenic action of the stem bark or its exudate.

• Toxicological Research
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• v.18 no.1
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.