• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.302-310
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• 2020

Botulinum toxins are neurotoxic modular proteins composed of a heavy chain and a light chain connected by a disulfide bond and are produced by Clostridium botulinum. Although lethally toxic, botulinum toxin in low doses is clinically effective in numerous medical conditions, including muscle spasticity, strabismus, hyperactive urinary bladder, excessive sweating, and migraine. Globally, several companies are now producing products containing botulinum toxin for medical and cosmetic purposes, including the reduction of facial wrinkles. To test the efficacy and toxicity of botulinum toxin, animal tests have been solely and widely used, resulting in the inevitable sacrifice of hundreds of animals. Hence, alternative methods are urgently required to replace animals in botulinum toxin testing. Here, the various alternative methods developed to test the toxicity and efficacy of botulinum toxins have been briefly reviewed and future perspectives have been detailed.

• Korean Journal of Veterinary Research
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• v.45 no.1
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• pp.29-37
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• 2005

13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.

• Toxicological Research
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• v.15 no.1
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• pp.103-107
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• 1999

In order to evaluate acute toxicity of Coptidis rhizoma, 6 week- and 13 week-old male ICR mice received Coptidis rhizoma extract (600~4,800 mg/kg body weight) orally, and toxicological responses were observed for consecutive 7 days. In the mice received relatively high concentration of Coptidis rhizoma($\geq$1,200mg/kg), death occurred within 3 hrs after oral administration, and its ratio in 13 week-old mice was conspicuously higher than that in 6 week-old mice. $LD_{50}$ of Coptidis rhizoma were estimated to bi 2,575 mg/kg and 1,490 mg/kg body weight in 6 week and 13 week-old mice, respectively. Coptidis rhizoma-treated animals manifested a variety of abnormal clinical findings such as ptosis, crouching, lethargy, convulsion, bizarre behavior and truning sideway. These abnormalities also ranked highly in the 13 week-old mice compared to those in the 6 week-old mice. In addition to abnormal behaviors, Coptidis rhizoma($\geq$1,200 mg/Kg) significantly elevated the urinary contents of bilirubin, urobilirubin, protein and glucose, and values in 13 week-old mice was higher than those in 6 week-old animals. No toxicological response was observed at concentration less than 600 mg/kg. Our results clearly demonstrate that susceptibility of mice to Coptidis rhizoma may be related with age, indicating that younger age mice is more resistant to the Coptidis rhizoma than the older, and toxicological mechanism of Coptidis rhizoma may be closely associated with its pharmacological mechanism.

• Herbal Formula Science
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• v.16 no.2
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• pp.163-169
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• 2008

The kidney toxicities of BDR-29 used for improvement of the vascular diseases, was examined using male and female Sprague-Dawley rats. The male and female rats were divided into 4 groups for intragastrical treatment with doses of 0, 5, 50, and 500 mg/kg/day for 13 weeks, respectively. In all male and female rats treated with BDR-29, no mortality and gross pathological findings were shown for 13 weeks. There substantially was no change in body weight in all rats with treatment of BDR-29. The renal functional parameters including urinary volume, urine osmolality, electrolytes excretory rate, creatinine clearance, and solute-free water reabsorption were not exchanged in all rats treated with BDR-29. Taken together, these results suggest that BDR-29 has no toxicity on kidney in all male and female rats.

• Journal of Environmental Health Sciences
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• v.19 no.4
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• pp.67-82
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• 1993

This study was performed to investigate the preventive effect of KDD against lead toxicity. KDD of 133, 266, 532 and 1,064 mg/kg were administered twice to the rats of Sprague-Dawley strain and then 300 mg/kg lead acetate was given to times, respectively. 1. The accumulation effects of KDD against to lead showed the changes of lead concentration by time variation. But, no statistical significance were showed on 8 and 10 weeks for kidney, spleen, 8 weeks for liver, and 4, 6 and 8 weeks for duodenum. In the femur, statistical significance existed during the whole experimental period. The relatively high concentration of lead detected in the feces of the experimental group means that KDD facilitated excretion of lead. 2. The histopathological effect of KDD against lead showed cytomegaly, karyomegaly, inclusion body, urinary cast and hemosiderin of kidney in the experimental group I (Pb 300 mg/kg). Recovery of KDD administrated group was inclined to increase by KDD concentration. But, spleen's histopathological recovery of KDD aginst to lead did not show as much as kidney. In conclusion, this study revealed the preventive effect of KDD against lead toxicity and its mechanism inferred to facilitate lead excretion in feces following hinderance of lead absorption in the gastric-intestine and organs.

• Toxicological Research
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• v.32 no.1
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• pp.57-64
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• 2016

Recently several studies reported that the renal toxicity of lead (Pb) and cadmium (Cd) may exist in even a low level exposure. In terms of the deterioration of tubular function, it affects the loss of divalent metals and leads to other complications, so renal tubular effect of heavy metals should be well managed. Considering the exposure to heavy metals in reality, it is hard to find the case that human is exposed to only one heavy metal. We designed a cross-sectional study using Korean Research Project on the Integrated Exposure Assessment (KRIEFS) data to investigate the renal effects of multiple metal exposure in general population. We used blood Pb and urinary Cd as exposure measures, and urinary N-acetyl-${\beta}$-D-glucosaminidase (NAG) and ${\beta}_2$-microglobulin (${\beta}_2$-MG) as renal tubular impairment outcome. We conducted linear regression to identify the association between each heavy metal and urinary NAG and ${\beta}_2$-MG. And then, we conducted linear regression including the interaction term. Of 1953 adults in KRIEFS (2010~2011), the geometric mean of blood Pb and urinary Cd concentration was $2.21{\mu}g/dL$ (geometric $SD=1.49{\mu}g/dL$) and $1.08{\mu}g/g\;cr$ (geometric $SD=1.98{\mu}g/g\;cr$), respectively. In urinary Cd, the strength of the association was also high after adjusting (urinary NAG: ${\beta}=0.44$, p < 0.001; urinary ${\beta}_2$-MG: ${\beta}=0.13$, p = 0.002). Finally, we identified the positive interactions for the two renal biomarkers. The interaction effect of the two heavy metals of ${\beta}_2$-MG was greater than that of NAG. It is very important in public health perspective if the low level exposure to multiple heavy metals has an interaction effect on kidney. More epidemiological studies for the interaction and toxicological studies on the mechanism are needed.

• Journal of Nutrition and Health
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• v.19 no.5
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• pp.323-332
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• 1986

This study was performed to see the effects of lead poisoning and dietary protein levels(6, 15 and 40 % casein diets) on growth, protein and lipid metabolisms in growing rats. It was also investigated whether the high protein intake would alleviate lead toxicity by decreasing Pb absorption and/or increasing Pb excretion. The results obtained were summarized as follows ; 1) Weight gain, F.E.R liver weight, weight and length of bone in Pb-administered groups were lower than in Pb-free groups. However, these values in the 40% casein diet group with Pb were increased to the level in 15% casein diet group without Pb. 2) Hematocrt and hemoglobin content in blood were lower in Pb -adminstered groups than in Pb free groups. Especially, these levels were lower in 6% casein diet group with Pb than in any other group. 3) Plasma protein level in th e 40% casein casein diet group was the highest of all groups and those of Pb-administered groups tended to be lower than those of Pb-free groups. Plasma lipid and cholesterol levels were increased with decreasing dietary protein level, and these levels were higher in the animals exposed to Pb than in free groups.4) Total liver protein, lipid and cholesterol contents were increased with increasing dietary protein level, and these contents were lower in Pb-administered groups than in Pb free groups. 5) Fecal Pb excretion was not different between 6 and 40% casein diet groups. However, urinary Pb excretion was higher in the 40% casein diet group than in the 6% casein diet group. Above results suggest that, in exposing to the Pb pollution, sufficient protien intake must be recommended. High protein intake seemed to alleviate lead toxicity by increasing urinary Pb excretion.

• Toxicological Research
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• v.16 no.1
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• pp.47-52
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• 2000

To evaluate the renal toxicity of the antitumor agent, 1-(N-methyl) piperazinyl-3-phenyl-isoquinoline(CWJ-$\alpha$-5), rats were terated with CWJ-$\alpha$-5 (acute : 100mg/kg, i.p., single and subacute : 10mg/kr, i.p., daily for 7 days). The changes in the body weights, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine, the activities of N-acetyl-$\beta$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), $\gamma$-glutamyl transpeptidase ($\gamma$-GT) and lactate dehydrogenase (LDH) in 24 hr urine were also determined. The body weight and water consumption were decreased after the acute and subacute administration. However, the excretion of urine was not changed except the 1 day after the acute treatment. The excretion of creatinine was significantly decreased from 1 day after acute administration and continuously decreased. Also the excretion of creatinine was decreased during subacute administration. However, the protein excretion did not changed in both treatment. Those indicate that CWJ-$\alpha$-5 might decrease the metabolic rate of muscle. The urinary activities of NAG, AAP, $\gamma$-GT, and LDH were significantly affected by the drug treatment. The urinary activities of NAG, AAP and $\gamma$-GT were significantly increased 1 and 3 days after the acute administration and then returned to the control value. However, the urinary activities of LDH were increased 7 days after acute treatment. During subacute treatment, the urinary activities of $\gamma$-GT were not changed. However, the urinary activities of NAG, AAP and LDH were only significantly increased after the third administration. These results indicate that either the high acute dose or the subacute administration with low dose of the compound might induce a temporal damage in the kidney cells.

• Journal of dental hygiene science
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• v.12 no.3
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• pp.253-258
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• 2012

Dental amalgam is an alloy composed of a mixture of approximately equal parts of elemental liquid mercury and an alloy powder. Amalgam has been the most popular and effective restorative material used in dentistry. Despite the long history and popularity of dental amalgam as a restorative material, there have been periodic concerns regarding the potential adverse health effects arising from exposure to mercury in amalgam. Since children are more at risk for mercury toxicity, we aimed to assess the association between dental amalgam filling and urinary mercury concentration in children. 581 of elementary school children in grades 1st4th were conveniently recruited from two schools located in Daegu city, Korea. To obtain dental caries experience states, oral examination were conducted using the full term for DFS index, number of amalgam filling surfaces and the type of filling materials. A questionnaire was used to collect information about general characteristics and the frequencies of tooth brushing, gum chewing and fish/seafood consumption. The statistical analysis was done using the SPSS 18.0 program. The mean urinary mercury concentration in children having more surfaces was highest. As a results Urinary mercury concentration of children who have 79 teeth of amalgam filling and more than 10 is higher than without amalgam filling. The number of amalgam filling surface is closely related with urinary mercury concentration.

• Journal of Pharmaceutical Investigation
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• v.9 no.3
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• pp.9-21
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• 1979

This study was undertaken to establish the different pharmaceutical properties between promethazine HCl and promethazine pamoate. First, promethazine pamoate was prepared by using the modified method of Saias. Second, in order to study the different pharmacokinetics between promethazine pamoate and promethazine HCl, absorption rate, plasma concentration, and distribution, as well as urinary excretion of the both compounds were examined in rabbits as an experimental animal: The results were as follows. 1. In the in vitro isolated intestine of rabbit, the rate constant for absorption of promethazine pamoate was $0.347hr^{-1}$ and that of promethazine HCl was $0.532hr^{-1}$. 2. After oral administration of promethazine pamoate, the increase of plasma concentration of promethazine was much slower than that of promethazine HCl. 3. The urinary excretion rate of promethazine pamoate was significantly low in comparison to that of promethazine-HCl; i. e. about 50% of promethazine HCl was excreted within 3 hours, and 5 to 15 hours for that of promethazine pamoate. 4. The tissue concentration of promethazine after oral administration of promethazine pamoate in rabbit was steadily increased for 5 hours. However, promethazine HCl concentration reached to maximum 1 hour after administration, then decreased slowly. 5. A significant amount of promethazine was mainly distributed in spleen, kidney, lung, liver and heart in this order, rather than other organs, such as brain, and muscle. 6. In the toxicity test by using mouse, $LD_{50}$ for promethazine pamoate was 3,250 mg/kg, while $LD_{50}$ for promethazien HCl was 298mg/kg.