• Toxicological Research
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• v.14 no.3
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• pp.401-409
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• 1998

Group of 40 male and 40 female ICR mice was given daily per oral treatment with the combination of enalapril plus Ginkgo biloba extract (EGb 761), 3+9mg/kg/day(low dosage group), 10+30mg/kg/day (middle dosage group), 30+90mg/kg/day (high dosage group) for 3 months in drinking water according to Established Regulation of Korean National Institute of Safety Research (1994. 4.14). Appearance, behavior, mortality, and food consumption of mouse of treated groups were not affected during the experimental periods. No significant the combination of enalapril plus Ginkgo biloba extract (EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight, Lung edema were observed and the weight of lung were increased in low dosage treated group of the male mice, which be associated with enalapril treatment, but these changes were not found in middle and high dosage group. Our results suggest that to toxic changes were found in rat treated orally with the combination of enalapril plus Ginko biloba extract (EGb 761) for 3 months.

• Toxicological Research
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• v.12 no.1
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• pp.47-52
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• 1996

The renal toxicity of the extract of Polygalae Radix was investigated in rats. Rats were treated with 3.5 mg/Kg of the extract, i.p., for 7 days. Changes in consumatory behavior, 24 hour-urine and the activities of urinary enzymes were determined during the administration of the extract. Significant decrease in body weight and food consumption and increase in 24 hour-urine volume were observed during the administration. However, the quantity of total creatinine in urine was decreased significantly. Those indicate that subacute treatment with the extract might induce diuresis and the ditiresis might be due to the decrease in water reabsorption. In the activities of urinary enzymes, the activities of alanine aminopejotidase (AAP) and gamma-glutamyl transpeptidase (GGT) were increased 4.3 and 3.5 times and then returned to the control. The activity of N-acetyl-${\beta}$-D-glucosaminidase (NAG) was increased 7.2 times and then decreased slowly. But, it was significantly higher than that of the control evea after the last administration. The activity of factate dehydrogenase (LDH) was increased continuozlsly during the treatment. It showed 32 times higher than the control. These results suggested that the extract of Polygalae Radix had toxic effect on kidney. Furthermore, the result suggested that the subacute administration of the extract induced resistance against the toxicity of Polygalae Radix.

• Toxicological Research
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• v.35 no.3
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• pp.233-239
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• 2019

Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.19-31
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• 1996

This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.

• Toxicological Research
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• v.14 no.3
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• pp.365-370
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• 1998

To evaluate the renal toxicity of the antitumor agent, p-{N,N,-Bis(2-chloroethyl)amino}-4-phenyl acetyl-amino-2,6-piperidinedione(CK-15), rats were treated with CK-15 (acute: 50mg/kg. i.p., single and subacute: 5mg/kg, i.p., daily for 7 days). The changes in the body weight, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine and portein, the activities of N-acetyl-${\beta}$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GT) and lactate dehydrogenase (LDH) in 24hr urine were also determined. The body weight, water consumption, and urine volume were decreased after the acute and subacute administration. However the weights of kidney were not changed after the treatments. The excretion of creatinine was significantly decreased 1 day after acute administration but, returned to the control value. In subactute administration, the excretion of creatinine was gradually decreased. However, the protein excretion did not changed in both treatment. Those indicate that CK-15 might decrease the metabolic rate of muscle. THe urinary activities of NAG, AAP, ${\gamma}$-GT, and LDH were significantly affected bythe drug treatment. The urinary activities of NAG, AAP and ${\gamma}$-GT were significantly increased 1 day after the acute administration and then returned to the control value. However, the urinary activities of LDH were not changed in acute treatment. In subacute treatment, although the urinary activities of NAG were not changed, those of AAP and ${\gamma}$-GT were significantly increased 2.3 times at 3 days during the subacute administration. Also the urinary activities of LDH were significantly increased at 7 day after the administration. These results indicate that the high and subacute administration might induce a damage in the kidney cells. Furthermore the present results suggest that the toxic effects of CK-15 might be due to the accumulation of the metabolites.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.226-235
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• 1993

DA-125, a new anthracycline antitumor antibiotic, was administered to Sprague-Dawley rats intravenously for 4 weeks to investigate the repeated dose toxicity Focal alopecia was noted in three female rats receiving 1.0mg/kg/day. In rats receiving 1.0 mg/kg/day, weight gain decreased in both sexes after first or second week. Hematological examination revealed lower counts of total leukocyte and increased numbers of platelet after second week. At terminal necropsy, atrophy of thymus and spleen was observed. Lymphocytic depletion of thymus and atrophy of white pulp in spleen were observed microscopically. A decrease in the number of hematopoietic cells in the bone marrow and degeneration of germinal epithelia in testes were also observed. These treatment-related effects were mainly confined to rats receiving 1.0 mg/kg/day. And toxic effects with microscopic changes were not observed in rats receiving 0.2 mg/kg/day or 0.04 mg/kg/day.

• Korean Journal of Pharmacognosy
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• v.19 no.4
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• pp.262-269
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• 1988

The Forsythiae fructus is described to be used as an antiinflammatory drug, diuretics, antidotes and antibacterials in oriental literatures. In order to investigate the efficacy of Forsythiae viridissima (Oleaceae), the methanol extract and its fraction have been evaluated for the acute toxicity, antiinflammatory, analgesic and spasmolytic action in animals. The methanol extract of Forsythiae fructus was found to have significant antiinflammatory activity in the acute and subacute antiinflammatory model in rats, but have no analgesic action. Furthermore, through fractionation procedure, it was found that the active compounds were easily soluble in chloroform and butanol. It is also noted that the extracts had spasmolytic activities in the rat fundus and uterus and had low acute toxicity in mice.

• Toxicological Research
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• v.18 no.1
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• pp.47-57
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• 2002

The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

• Toxicological Research
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• v.18 no.1
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• pp.31-41
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• 2002

The present study was conducted to investigate the potential subacute toxicity of plant sterol esters by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to rats at dose levels of 0, 1000, 3000, and 9000 mg/kg/day for 4 weeks. During the test period, clinical sign, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. A reduction in the body weight was observed in females of the 9000 mg/kg group on day 27 after the initiation of treatment, but not in males of the group. There were no treatment-related effects on mortality, clinical sign, food and water consumption, ophthalmoscopy, urinarlysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. Based on these results, it was concluded that the 4-week repeated oral dose of plant sterol esters resulted in suppressed body weight in female rats at a dose level of 9000 mg/kg/day. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 9000 mg/kg/day for males and 5000 mg/kg/day for females.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.10
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• pp.1264-1270
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• 2008

In order to evaluate their possible subacute toxicity, the male and female of SD rats were given to 30 kGy irradiated cereal powders for three months. During the experimental periods, appearance, behavior, mortality, body weight, organ weight, and food consumption of rats fed the 30 kGy cereal powders were not affected compared to the non-irradiated control. In urine analysis, histopathological examination, hematological as well as in serum biochemical findings, no significant differences were found between the rats administered with non-irradiated control and 30 kGy cereal powders for three months. These results indicate that cereal powders irradiated at 30 kGy did not show any toxic effects under these experimental conditions.