This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.
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.
Objectives : This study was done to investigate the effects of JMT on hypothyroidism in rats. Materials and Methods : After pretreatment with 50mg/kg thiouracil for 30 days, the experimental group was treated with 0.56g/kg JMT orally and the control group was treated with 0.56g/kg of normal saline instead for 20 days. The various indicators related to hypothyroidism were measured, such as T3-uptake content, T3 content, T4 content, TSH content, hematological values, enzyme activity, total cholesterol content, Na+ content change in the serum and body weight of rats induced by thiouracil. Results : The JMT-treated group showed significant increase in comparison with the control group in serum T3-uptake and T4 content. The JMT-treated group also showed significant decrease in comparison with the control group in serum TSH content. However, the JMT-treated group did not show significant increase in comparison with the control group in serum T3 content. The JMT-treated group showed significant increase in comparison with the control group in serum RBC. The JMT-treated group showed significant decrease in comparison with the control group in serum CPK, ALP, LDH content and serum total cholesterol content. The JMT-treated group did not show significant increase in comparison with the control group in serum Na+ content. The JMT-treated group showed significant decrease in comparison with the control group in body weight. Conclusions : These results suggest that JMT is useful in treatment of hypothyroidism.
This study was performed to obtain an accurate methods of diagnosis in early stage of traumatic pericarditis and myocarditis in ruminants. Korean native goats were used as experimental animal and traumatic pericarditis and myocarditis were induced by surgical intervention. The changes in clinical signs, hematological values, blood enzymes and electrocardigrams were observed for 14 days after operation. The results obtained were as follows: 1. Body temperature in experimental group of induced traumatic pericarditis and myocarditis was slightly increased than control group that was rumenotomized. Heart rate was increased in both groups but the increased rate was noticed remarkably in experimental group. There was no change in respiratory rate in experimental and control group. 2. Total leucocytes counts and neutrophil percentage maintained higher level after operation and lymphocytes percentage noticed reversed proportion to neutrophil in both groups. 3. Serum total protein concentration and alkaline phosphatase activities after operation showed a little lower levels than these values prior to operation. Serum glutamic oxaloacetic transaminase and lactic dehydrogenase activities in control group showed slight increase through all the experimental period, while in experimental group these activities were markedly elevated and an increase in serum lactic dehydrogenase activities was more remarkable comparing to serum glutamic oxaloacetic transaminase. 4. Electrocardiograms in control group did not show any abnormalities except for slight increase in heart rate. In experimental group the amplitude of QRS complex was increased in duration of experimental period. The transference from QRS complex to T wave was uncertain and S-T segment moved upward obliquely through electrical zero line.
The traumatic hepatitis and splenitis were experimentally induced in Korean native goats. General examinations, hematological and blood biochemical findings were investigated up to 10 days after induction of traumatic hepatitis and splenitis. Body weight of goats with traumatic hepatitis and splenitis showed no change or only a slight decrease. Changes in body temperature and respiratory rate were not noted in both experimental groups. Heart rate hart not been changed in traumatic splenitis group but were a little increased in traumatic hepatitis group. Erythrocytic series such as erythrocyte counts, hemoglobin concentration and packed cell volume showed same variation within normal range during the period of observation. Total leucocyte counts showed the considerable increase in both experimental groups. The increase of the percentage of neutrophil and the decrease of the percentage of lymphocyte were more remarkable in traumatic hepatitis group than that of traumatic splenitis group. Serum aspartate transferase activity was increased in both experimental groups after surgery, while serum alkaline phosphatase activity has been decreased conciderably up to 7 days after surgery. Serum lactic dehydrogenase activity has been increased up to 3 days after operation and thereafter the activity has returned to normal level in traumatic hepatitis group and the activity increased only the first day after surgery in traumatic splenitis group. There were no changes in total protein and albumin contents in both experimental groups during the period of observation. Serum total cholesterol contents showed a slight increase in both experimental groups and the range of increase in traumatic hepatitis group was more wide. Serum bilirubin contents were net changed in traumatic hepatitis group, but showed a slight increase in traumatic splenitis group.
We performed this study to determine the effect of Bu-Zhong-Yi-Qi-Tang, as a prescription of traditional Oriental medicine, and its major ingredients on jejunal crypt survival, endogenous spleen colony formation, apopotosis in jejunal crypt cells, lethality and hematological change of mice irradiated with high and low dose of Y-radiation. Bu-Zhong-Yi-Qi-Tang administration before irradiation protected the jejunal crypts (p<0.0001), increased the formation of endogenous spleen colony (p<0.05) and reduced the frequency of radiation-induced apoptosis (p<0.05). The survival rate and mean survival time of the groups treated with Bu-Zhong-Yi-Qi-Tang within 30 days after the treatment were far better than the irradiation control group. In the experiment on the effect of ingredients of Bu-Zhong-Yi-Qi-Tang, the result indicated that the extract of Rensan (Panax ginseng), Danggui (Angelica sinensis), Shengma (Cimicifuga heracleifolia) and Chaihu (Bupleurum falcatnosa) might have a major radioprotective effect. Although the mechanisms of this inhibitory effect remain to be elucidated, these results indicated that BU-Zhong-Yi-Qi-Tang might be a useful radioprotector, especially since it is a relatively nontoxic natural product. Further studies are needed to characterize better the protective nature of Bu-Zhong-Yi-Qi-Tang extract and its ingredients.
Objectives : In the present study, we investigated whether or not an herb mixture including Lycii fructus(HML) has attenuation effects on light stress in rats. Methods : Light stress was induced by exposure to 300 lx of constant lifht for 24 h and 1mg/kg of caffeine was injected into the rat. Rats were orally treated with distilled water of HML for 21 days at 100mg/kg/d. The changes of mortality rate, clinical signs, body, blood chemistry, melatonin and IL-2 expression were analyzed after experiment. Results : Normal weight changes were observed in all treatment groups. In addition, no changes were observed in dead animals and general symptoms. At the time of autopsy, the appearance of all groups and gross examination of major organs were observed, and no gross findings were observed. Blood biochemical tests showed that total cholesterol and HDL cholesterol levels were statistically significantly decreased in the group treated with HML compared to the stress-induced group. Melatonin was measured in the blood, but there was no significant difference in the group treated with HML compared to the group with stress-induced group, but it tended to increase. IL-2 was measured in the blood, no significant change was observed in the group treated with HML compared to the stress-induced group. Conclusions : According to the above results, HML maybe help with hematological changes expressed by caffeine and light-induced stress.
Objectives : This experiment was designed to assess the single oral toxicity of Ethanol Extract Inulae Flos (IF) ethanol extracts. IF is one of the important herbs to remove phlegmy which is the viscous turbid pathological product that can accumulate in the body, causing a variety of diseases. Nevertheless, there has been a lack of research on the pharmacology toxicity of IF. Methods : In this study, IF was orally administered to 5 weeks ICR mice as an oral dose of 2,000 or 3,000 or 5,000 mg/kg. The condition of the mice was observed for 14 days and their weights were measured every two days. Results : None of the mice died for 14 days. The abnormal clinical symptoms and anatomical signs of toxicity were not found in any treatment groups. The gain of net body weight was observed. There was also no significant difference in the organ weight. The serum biochemistry and hematological analysis showed a decrease in BUN, red blood cells, white blood cells and platelets although within the normal ranges. Conclusions : These results suggest that the 50% lethal dose of IF is more than 5,000 mg/kg. This could be thought that IF is a safe drug without acute toxicity and side effects. However, IF showed some weight loss and change in blood test, so it will need to be careful when using it for high doses.
This study investigated the survival rates and physiological responses of Korean rockfish, Sebastes schlegeli, in live fish containers ($8^{\circ}C$, 33 psu) for 18 days. The survival rate was 99% and 97% in the control and experimental groups, respectively. Hematocrit and hemoglobin did not differ significantly between the control and experimental groups. Glucose and cortisol rose immediately on the first day of containment, but both gradually normalized. Aspartate aminotransferase and alanine aminotransferase did not differ significantly between the two groups after recovery. $NH_3$ continued to rise after the first day, but decreased to a level not significantly different from that of the control group during the recovery period. Plasma ions and osmolality did not change abnormally. The hemocyte population was not significantly different from that of the control. The ratios of apoptotic and necrotic cells indicated no specific variation in hemocyte viability. The histological changes in the skin and gills were not significantly different from those seen in the control. The experimental data obtained in this study suggest that live fish containers may be used to transport Korean rockfish without significantly affecting their physiology or survival.
We studied the acute oral toxicity of black ginseng (BG) produced by heat process in rats. Single acute BG extract doses of 0, 5, 10, and 15 g/kg dissolved in saline were administered by oral gavage and the animals were kept under observation for 14 days. The single administration of BG extract up to 15 g/kg did not produce mortality, behavioral change or abnormal clinical signs in the rats. These results indicated that the oral $LD_{50}$ of the BG extract in the rats is higher than 15 g/kg. Compared to the control group, no treatment-related biologically significant effects of BG extract were noted in the measurements of the body weight or food intake. At the end of the period, the biochemical parameters and hematological parameters were analyzed in the plasma and blood. A histopathological examination of the liver and kidney was also conducted. Only the blood nitrogen urea and potassium levels in the biochemical indices showed significant differences at 10 and 15 g/kg doses of BG extract compared to the control group. These changes were not considered to be due to the toxicity. None of the other clinical chemistry parameters were affected. Therefore, these results indicate that the BG by heat processing is virtually nontoxic.
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