• Journal of Life Science
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• v.15 no.3 s.70
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• pp.461-467
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• 2005

This study was conducted to investigate the biological activity and hepatoprotective effect of DWP-04 [DDB : selenium yeast: glutathione (31.1 : 6.8 : 62.1(w/w/w)] in D-galactosamine (GaIN) intoxicated rats. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was orally administered everyday before the start of GaIN injection (400 mg/kg, ip) for two weeks and animal decapitated for 24 hrs after GaIN­injected. The activities of serum enzymes, markers of liver function, were increased in the GaIN group compared to normal group and significantly lowered in the DWP-04 pretreated group than in the GaIN group. Hepatic lipid peroxide level and activities of phase 1 enzymes were significantly higher than those of GaIN group compared to normal group and lower in the DWP-04 pretreated group than in the GaIN group, and phase II enzyme activities in liver were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Total hepatic glutathione content and glutathione biosynthesis enzymes were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Therefore, the current results indicated that DWP-04 administration alleviated the GaIN-induced adverse effect through enhancing the antioxidant enzyme activities.

• Korean Journal of Pharmacognosy
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• v.36 no.2 s.141
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• pp.81-87
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• 2005

The effects of the DWP-04 [DDB:selenium yeast:glutathione (31.1 : 6.8 : 62.1 (w/w%)] on acetaminophen detoxification enzyme system were studied in rats. Treatment with DWP-04 was prevented againt acetaminophen-induiced hepatotoxicity in rat as evidenced by the decreased formation of lipid peroxide. Effect of DWP-04 on the activities of free radical-generating enzymes, free radical scavenging enzymes and glutathione-related enzymes as well as detoxification mechanism of DWP-04 against acetaminophen-treated was investigated in rat. Activities of cytochrome p450, cytochrome b5, aminopyrine demethylase and aniline hydroxylase as free radical-generating enzymes activities were decreased by the treatment with DWP-04 against acetaminophen treated. Although acetaminophen-induced hepatotoxicity results in the significantly decrease in the level of hepatic glutathione and activities of glutathine S-transferase, quinone reductase, glutathione reductase and ${\gamma}-glutamyl-$cysteine synthetase, these decreasing effects were markedly lowered in the DWP-04-treated rat. Therefore, it was concluded that the mechanism for the observed preventive effect of DWP-04 against the acetaminophen-induced hepatotoxicity was associated with the decreased activities in the free radical-generating enzyme system.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.44-49
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• 2005

The protective effects of the DWP-04 [DDB : selenium yeast: glutathione {31.1 : 6.8 : 62.1 (%, w/w)} against hepatotoxicity by carbon tetrachloride $(CCl_4)$ were studied in rats. The rats were intraperitoneally injected with $CCl_4$ (50% in com oil) at initial dose of 1 ml/kg followed by 0.5 ml/kg 3 times during 1 week. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was administered everyday before the start of $CCl_4$ injection for two weeks. $CCl_4$ induced hepatocelluar degeneration and necrosis, which led to a great increase in serum aminotransferase, alkaline phosphatase activity and serum lipid levels. It was found by biochemical analysis that $CCl_4$ treatment remarkably increased thiobarbituric acid reactive substances and physphatidylcholine hydroperoxide in hepatic tissues and induced antioxidant enzymes such as catalase and superoxide dismutase (SOD). Liver and serum lipids were significantly lower in rats fed on DWP-04 than in rats induced by $CCl_4$ only-treatment. These results suggested that the DWP-04 could be a promising candidate for the protection of liver injury based on the preventive effects against lipid peroxidation and serum biochemical parameters.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.138-147
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• 1996

DWP401, a recombinant human epidermal growth factor, was subcutaneously administered to ICR mice at the dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day (15rats/sex/group) in order to evaluate the subchronic toxicity. General observations, examinations for food and water consumption, ophthalmoscopy and urinalysis were carried out during the study. For the complete gross and microscopic examinations, 10 mice/ sex/group were sacrificed at the ends of the dosing period, and the remaining animals were sacrificed with a 5 week recovery period. Examinations for hematology and blood biochemistry were also carried out at the time of recovery period. Based on the results, it was thought that the target tissue or organs were mesothelial cell, injection site, spleen, adrenal gland, ovary and transitional epithelial cell of urinary tract, and no observed toxic level of DWP401 was 0.04 mg/kg while definite toxic dose level might be 0.2 mg/kg.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.328-336
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• 1998

The subacute oral toxicity study of DWP-311 was carried out in Sprague-Dawley rats of both sexes. We daily examined clinical signs, body weights, hematological and biochemical parameters, and histopathological examinations for 30 days after administration of DWP-311 with different dose levels (0, 0.04, 0.2, and 1.0 g/kg). There were no clinical signs and pathological changes compared with control group except slight decreases in spontaneous motor activities and locomotions at high dose group of DWP-311. Body weights were not significantly changed in animals treated with DWP-311, In histopathological examinations, there were 2 cases of pneumonia in control group for one male and one female, but it was not directly related to DWP-311. These results indicate that subacute oral toxicities of DWP-311 were low and the no-observed a dverse effect level (NOAEL) was considered to be 1.0 g/kg in rats.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.122-122
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• 1995

본 연구는 유전공학적인 방법으로 합성된 상피세포성장호르몬인 DWP-401에 대한 마우스의 반복투여에 의한 아급성독성을 조사하기 위하여 실시하였다. 시험군은 ICR 마우스 압수 각각 10 마리씩으로 하여 3 개의 처치군 및 대조군(0, 1, 0.2, 0.04 mg/kg)과 회복시험군(0, 1 mg/kg)을 두었다. 시험물질은 13 주간 경배 부 피하에 1 주에 6 회의 빈도로 투여하였고 대조군과 최고용량 군에서 5 주간의 회복기간을 두었다. 시험기간 중 체중, 사료섭취량 및 음수섭취량을 측정하였고, 뇨검사, 안검사, 혈액학적검사, 혈액생화학적 검사, 부검소견관찰, 장기중량측정 및 병리조직학적검사를 실시하였다. 이상의 실험결과 DWP-401의 마우스에 대한 표적장기는 상피세포, 간장, 비장, 부신, 방광 신장, 각 장기의 복막과 흉막, 림프계, 난소 및 투여부위였고 회복성이 인정되었다. 무해용량은 0.04 mg/kg/day였으며 확실 중독량은 0.2 mg/kg/day 이상으로 사료되었다.