• Herbal Formula Science
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• v.20 no.2
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• pp.55-63
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• 2012

Objectives : This study was conducted to investigate the safety of Bangpungtongsung-san in rats. Methods : The safety of this prescription on acute toxicity was evaluated by single dose toxicity study. Rats were orally administrated in a single dose of 0 and 2,000 mg/kg(limited dose) Bangpungtongsung-san. There were 7 rats in each groups. All animals were sacrificed after 14 days of treatment. After single administration, mortality, clinical signs, and body weight changes were observed for 14 days. Three parameters(autopsy finding, clinical chemistry, and hematology) were tested on the last day. Results : In this study with rats, Bangpungtongsung-san treatment did not show any acute toxicity. No mortality was noted for 14 days of treatment. There were no adverse effects on clinical signs, body weight changes, and autopsy finding at all treatment groups. The clinical chemistry parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. Conclusions : It is considered that $LD_{50}$ of Bangpungtongsung-san is over 2,000 mg/kg in oral administration by rats. This finding of the safety of Bangpungtongsung-san is expected to strengthen the position of this prescription as nontoxic medicine.

• Toxicological Research
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• v.17 no.4
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• pp.317-323
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• 2001

The skin penetration rate of methidathion in vitro and pharmacokinetics of methidathion in vivo were studied with male Sprague-Dawley rats by dermal treatment. The in vitro skin penetration rates for Sprague-Dawley rats of methidathion technical (50 mg, 100 ${mu}ell$) and emulsifable concentrate (EC,40mg, 100${mu}ell$) were determined as 18.4 $\mu\textrm{g}$/c $m^2$/h (RSD : 6.5) and 18.5 $\mu\textrm{g}$/c $m^2$/h (RSD : 3.2), respectively. Dose-related systemic exposure (AUC) was observed in rats after dermal treatment. The corresponding AUC, $T_{max}$, $C_{max}$, and $T_{1}$2/ of methidathion in plasma were 1.5$\mu\textrm{g}$.hr/ml, 6 h, 0.10 $\mu\textrm{g}$/ml, and 16 h, for 116mg/kg doses, 3.2 $\mu\textrm{g}$. hr/ml, 8 h, 0.12 $\mu\textrm{g}$/ml, and 23 h, for 232 mg/kg doses and 10 $\mu\textrm{g}$. hr/ml, 12 h, 0.32 $\mu\textrm{g}$/ml, and 20 h, for 1,160 mg/kg doses respectively. The urinary excretion of methidathion, estimated wing an equation derived from the in vitro skin penetration study was 0.24~0.35% of the absorbed dose. The concentration of methidathion in kidney was higher than that in liver. Dose-dependent absorption and excretion of methidathion without saturation was observed under in vivo experimental condition.n.n.

• Toxicological Research
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• v.8 no.2
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• pp.205-216
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• 1992

cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R), an antitumor platinum complex, was selected for clinical evaluation on the basis of its experimental antitumor and toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, orgnas which are mainly affected, and to estimate its lethality in mice and rats given SKI 2053R through two routes of administration. In male and female rats given a single intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were over 3.00g/kg, respectively. In male and female mice given a signle intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were 2.44g/kg and 1.59g/kg, respectively, In a single intraperitoneal dose of SKI 2053R, we determined that $LD_{50}$ values of male and female rats were 227mg/kg and 182mg/kg, and those of male and female mice were 198mg/kg and 207mg/kg, respectively. In gross and histopathological examinations on dead animals, we found that kidney and liver were mainly affected.

• Journal of The Korean Society of Clinical Toxicology
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• v.15 no.2
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• pp.122-130
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• 2017

Purpose: To evaluate the effects of low-dose intravenous N-acetylcysteine on the prevention of contrast-induced nephropathy (CIN) in patients undergoing computed tomography (CT). Methods: All patients presenting to our emergency department and undergoing CT with intravenous contrast media between August 2014 and April 2016 were retrospectively enrolled. We included hospitalized patients with renal dysfunction [estimated glomerular filtration rate (GFR) between 30 and $89mL/min/1.73m^2$]. A 600-mg injection of N-acetylcysteine was given to patients once before and once immediately after CT, depending on the preference of physician. The primary outcome was CIN defined as an increase in creatinine level of ${\geq}25%$ or ${\geq}0.5mg/dL$ from the baseline within 48 to 72 hours after CT. A trained person blindly reviewed all medical records. Results: Of the 1903 admitted patients, CIN occurred in 9.8% of patients who received 1200 mg intravenous N-acetylcysteine (24/244) and 6.8% of patients who did not (113/1659, p=0.090). In a multivariable regression analysis, N-acetylcystine was not relevant to the prevention of CIN (odds ratio=1.42 [95% CI, 0.90-2.26]). Even in the stratified analysis using the propensity score matching, N-acetylcysteine was irrelevant (GFR 30-59: odds ratio=1.06 [95% CI, 0.43-2.60]; GFR 60-89: odds ratio=1.76 [95% CI, 0.75-4.14]). After adjustment, crystalloids were significantly associated with the reduction in CIN compared with dextrose water (odds ratio=0.60 [95% CI, 0.37-0.97]). Conclusion: No effect was found when low-dose intravenous N-acetylcysteine was used to prevent CIN. However, there seems to be an association between crystalloids and reduction in CIN.

• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.310-315
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• 1994

The pharmacokinetics and tissue distribution of DA-3030 (recombinant human granulocyte colony-stimulating factor, rhG-CSF, recently manufactured by Dong-A research laboratory of Dong-A Pharmaceutical Company) were compared with reported data in the literature. After intravenous(i.v.) administration of DA-3030, at dose of 5, 10 and 100 $\mu\textrm{g}$/kg to rats, some pharmacokinetic parameters, such as terminal half-lives(1.05, 1.19 and 1.83 hr, respectively) and clearance (84.0, 54.8 and 45.5 mι/hr/kg, repectively), were dose-dependent. This could be due to the saturable metabolism of DA-3030 in rats. Similar results were also reported. After subcutaneous(s.c.) and intramuscular(i.m.) administrations of DA-3030, 10 $\mu\textrm{g}$/kg to rats, the extent of bioavailability(absolute bioavailability) were incomplete; the values were 23.3 and 18.2% after s.c. and i.m. injections, respectively, due to the degradation of DA-3030 by protease. After 7-consecutive day i.v. administrations of DA-3030, 10 $\mu\textrm{g}$/kg/day, to rats, the plasma concentrations and pharmacokinetic parameters of DA-3030 were not significantly different from those in single administration. In mice and dogs at DA-3030 dose of 10 $\mu\textrm{g}$/kg, the plasma concentrations of DA-3030 were also declined rapidly with terminal half-lives of 1.31 and 1.15 hr, respectively. DA-3030 was highly concentrated in the kidney after i.v. administration of DA-3030, 10 $\mu\textrm{g}$/kg, to rats, and the results were similar to those obtained using radiolabelled rhG-CSF in the literature. Above data indicate that DA-3030 has similar properties to rhG-CSF manufactured by other companies in view of pharmacokinetics.

• Journal of Acupuncture Research
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• v.36 no.3
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• pp.147-153
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• 2019

Background: The aim of this study was to investigate the safety and analgesic effects of Datura Flos pharmacopuncture (DFP). Methods: The analgesic effects of DFP were assessed using mechanical (hot plate), chemical (formalin test), and thermal (von Frey filament test) pain tests. Forty male Sprague Dawley rats were assigned randomly into DFP (75 mg/kg, 150 mg/kg), lidocaine 0.5%, or normal saline group for treatment on Kl3. Gross pathology, histopathology, biochemistry and hematology were performed. Results: In the hot plate test, DFP at a high dose (HDDFP; 150 mg/kg) produced a significant analgesic effect, at 10 and 20-minutes post injection (p < 0.01). Low dose DFP (LDDFP; 75 mg/kg) also showed an analgesic effect at 10 minutes post injection (p < 0.01). In the formalin test, HDDFP produced an analgesic effect, for 0-10 and 10-20 minutes (p < 0.01) post treatment, whereas LDDFP showed analgesic effects between 10-20 minutes (p < 0.05). In the von Frey filament test, DF-H produced an analgesic effect, 10 (p < 0.01) and 20 minutes post treatment (p < 0.05). LDDFP showed analgesic effect at 10 minutes (p < 0.05). In the acupuncture response test, HDDFP produced an analgesic effect at 10 minutes post treatment (p < 0.05). DF-H did not cause any anatomical changes to the liver or kidney and there were no abnormalities in biochemistry or hematology. Conclusion: DF-H was not toxic and provided short term analgesia, suggesting it may be useful in the management of pain.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.69-77
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• 2021

Propofol infusion syndrome characterized by rhabdomyolysis, metabolic acidosis, kidney, and heart failure has been reported in long-term propofol use for sedation. It has been reported that intracellular adenosine triphosphate (ATP) is reduced in rhabdomyolysis. The study aims to investigate the protective effect of ATP against possible skeletal muscle damage of propofol in albino Wistar male rats biochemically and histopathologically. PA-50 (n = 6) and PA-100 (n = 6) groups of animals was injected intraperitoneally to 4 mg/kg ATP. An equal volume (0.5 ml) of distilled water was administered intraperitoneally to the P-50, P-100, and HG groups. One hour after the administration of ATP and distilled water, 50 mg/kg propofol was injected intraperitoneally to the P-50 and PA-50 groups. This procedure was repeated once a day for 30 days. The dose of 100 mg/kg propofol was injected intraperitoneally to the P-100 and PA-100 groups. This procedure was performed three times with an interval of 1 days. Our experimental results showed that propofol increased serum CK, CK-MB, creatinine, BUN, TP I, ALT, AST levels, and muscle tissue MDA levels at 100 mg/kg compared to 50 mg/kg and decreased tGSH levels. At a dose of 100 mg/kg, propofol caused more severe histopathological damage compared to 50 mg/kg. It was found that ATP prevented propofol-induced muscle damage and organ dysfunction at a dose of 50 mg/kg at a higher level compared to 100 mg/kg. ATP may be useful in the treatment of propofol-induced rhabdomyolysis and multiple organ damage.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.5
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• pp.2180-2186
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• 2011

To find out the protective effects of Kamdootang against accumulation of cadmium in rats, the experimental rats were divided into 2 groups. One group was administered with cadmium alone and the other group administered with cadmium mixed with Kamdootang. Each group has been orally administered with different doses of cadmium such as 1.7 ${\mu}g/g/day$, 3.4 ${\mu}g/g/day$ and 6.8 ${\mu}g/g/day$, respectively, for 1 to 8 weeks. As a results, body weight gained has a tendency to decrease more in the Kamdootang treated groups and non-treated groups than in control group. Cadmium accumulation in kidney showed a significant difference between the Kamdootang treated group and Kamdootang non-treated group. As the experiment period is longer and longer, both groups have got more significantly cadmium accumulation amounts. The kidney system was researched through histopathological observation that Multiple foci of necrosis, hemorrhagic necrosis in glomeruli and cloudy swelling of tubules in kamdootang non-treated group. but tissue lesion of kidney was showed less kamdootang treated group than Kamdootang non-treated group. As remarked above results, when dose low concentrated Cd in rat, Kamdootang was reduced accumulation of Cd. in kidney.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.474-483
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• 2004

To know the effects between Cd inhalation toxicity and extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol in air using whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 1.03㎎/㎥ and mass median diameter(MMD) was 1.69㎛. 3 different dose intraperitoneal injections of extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group I and the highest lung and liver weight were also from inhalation exposure group I. The highest kidney weight was from inhalation exposure group III. The lowest Cd content in lung was 33.49㎍/g from inhalation exposure group I. The lowest Cd concentration in blood was 9.36㎍/㎗ from inhalation exposure control. Cd concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. The lowest Cd concentration in liver was 21.08㎍/g from inhalation exposure group III and The lowest Cd concentration in kidney was 15.78㎍/g from inhalation exposure group II. For weekly Cd concentration in urine, the value of the fourth week from inhalation exposure group III was the highest. For weekly Cd concentration in feces, the value of the first week from inhalation exposure group III was the highest. The highest metallothionein concentration in lung was 53.42 ㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 188.18㎍/g from inhalation exposure group III. The highest metallothionein concentration in kidney was 143.92㎍/g from inhalation exposure group III. The highest Hct, Hb, and WBC values were from inhalation exposure group II and the highest RBC value was from inhalation exposure group III.

• Journal of Ginseng Research
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• v.40 no.2
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• pp.135-140
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• 2016

Background: Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods: The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results: The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion: FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNKep53ecaspase-3 signaling cascade.