• Korean Journal of Pharmacognosy
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• v.21 no.2
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• pp.179-185
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• 1990

The acute and subacute toxicities and pharmacological actions of two preparations of Ssanghwa Tang prescriptions have been evaluated in mice, rats and rabbits. The two prescriptions were found to be safe drugs because those preparations exhibited almost no acute and subacute toxicities even at a high dosage level. The two prescriptions elicited CNS depressant activities characterized by potentiation of hexobarbital-induced narcosis, antipyretic activity in typhoid-vaccinated rabbits and a significant antifatigue effect against cold immobilized stress, the activities of prescription B being more potent.

• YAKHAK HOEJI
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• v.26 no.4
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• pp.209-214
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• 1982

Acute toxicities of purified ginseng saponin (PGS) in mice, and sbacute toxicities of PGS in rats were investigated. Average lethal doses ($LD_{50}$) of PGS in male mice were 270mg/kg (i.v.), 342mg/kg (i.p.), 505mg/kg (i.m.), 950mg/kg (s.c.), and more than 5,000mg/kg (p.o.), respectively. Results of subacute toxicity of PGS was as follows. Body weight was markedly increased by administration of PGS 7.7mg/kg but side effects were shown by administration of 77mg/kg and above dose. Especially administration of PGS 240mg/kg caused a marked decrease of albumin/globulin ratio, and 28% increase of urea nitrogen in serum, as well as 33% increase of liver weight/body weight ratio.

• Toxicological Research
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• v.6 no.1
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• pp.41-49
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• 1990

Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.213-213
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• 1996

The effects of the anti-tumor agent, SDZ-y2434, on rat kidney were investigated to predict the toxicities of its derivatives and to develope less toxic derivatives. After adjusted in metabolic cages for 5 days, rats were treated SDZ-62434(acute : 25mg/kg, i.p, once and 50mg/kg, i.p., once; subacute ; 10mg/kg, i.p., daily for 7 days). Kidney weights and urine volume during the treatment were observed. Creatinine concentration, protein concentration and the activities of N-acetyl-${\beta}$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), ${\gamma}$-glutamyl transpeptidase (GGT) and lactate dehydrogenase(LDH) in 24 hr urine were also determined. The kidney weights after the acute and subacute administration didn't show any difference. Urine volume increased 5 days after the acute administration (50mg/kg) and 3 days after the subacute administration. The excretion of creatinine was increased 5 days after the acute (50mg/kg) and subacute administration. However, the protein excretion didn't show any change. NAG acivity declined 7 days after the subacute administration. AAP and GGT activites increased 3 days after the acute administration (50mg/kg) but, returned to the control value. LDH activity showed continuousely high value after the subacute administration. These results indicates that the acute administration of SDZ-62434 might damage on glomerulus and that the subacute administration might be cytotoxic to kidney cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.1
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• pp.29-34
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• 2015

The objective of this study was to obtain data on the safety-in-use of nano calcium as a dietary supplement by assessing its acute and subacute oral toxicities in female and male Sprague-Dawley rats. A single oral dose of 5,000 mg/kg of nano calcium did not result in mortality or significant changes in the general behavior and gross appearance of the internal organs of rats. For subacute toxicity study, nano calcium was administered orally at a dose of 1,000 mg/kg daily for 14 days. There were no significant differences in organ weights between control and treated groups of both sexes. Hematological analysis and blood chemistry revealed no toxic effects of nano calcium. Pathologically, neither gross abnormalities nor histopathological changes were observed. These results show that nano calcium possesses very low toxicity as indicated in a rat model.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1025-1034
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• 2009

This study was carried out to examine the protective effect of Cultured Wild Ginseng(CWG) on the acute and subacute toxicities induced by doxorubicin(Doxo) in mice. Heart and liver weight was decreased following Doxo administration. In contrast, such a decrease was significantly attenuated by CWG administration. The value of serum CPK in Doxo group was increased compared with normal group. But the value of CWG group were decreased significantly compared with the values of Doxo group in the liver of the Doxo group, cloudy swelling of hepatic cells and narrowing of sinusoids were observed. Whereas in the CWG group, well oriented hepatic cell cords and sinusoids were observed. In the testis of the Doxo group, necrotic and degenerative changes of the seminiferous tubules, especially beneath testicular membrane were observed. But those lesions were alleviated in CWG group. Cross sectional area of testis and diameter of semineferous tubule were significantly increased in CWG group compared with Doxo group. Body weight was reduced in Doxo group compared with normal group. In contrast, such a decrease was significantly attenuated by CWG administration atwa5th day. Spermatogenetic cells in seminiferous tubules were necrotic and desquamated and the cellularity of seminiferous epithelia was reduced in Doxo group. But those lesions were attenuated by CWG administration. Cross sectional area of testis and diameter of seminiferous tubule were significantly increased in CWG group compared with Doxo group. In addition, the increase in lipid peroxidation(LPO) in testis was inaddition, the, iout such a increased was significantly inhibited in CWG group. BrdU labelled cells in the seminiferous tubules were remarkably decreased in Doxo group. Whereas the number of seminiferous tubules labelled with BrdU in spermatogonia was increased by CWG administration. The obtained results suggest that CWG has protective effect on doxorubicin-induced toxicity. This effect might be mediated through the supplementation of vital energy.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.867-870
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• 2001

All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

• Journal of Korean Neurosurgical Society
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• v.45 no.5
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• pp.275-283
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• 2009

Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.171-181
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• 1998

DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.