• Biomedical Science Letters
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• v.6 no.3
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• pp.193-199
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• 2000

To evaluate an effect of aging on the xylene toxicity, 50% m-xylene in olive oil (0.25 ml/100 g body wt.) was administered to 5 week and 12 week-old rats one times intraperitoneally and sacrificed at 24 hrs afterwards. The increasing rate of urinary m-methylhippuric acid concentration was higher in 12 week-old rats than 5 week-old rats by the treatment of m-xylene. On the liver function findings, i.e., liver weigh/body weight (%), serum levels of ALT activity and hepatic malondialdehyde content, 12 week-old rats showed more severe liver injury than 5 weeks those in xylene-treated rats. And the hepatic cytochrome P-450 contents was higher in 12 weeks rats than those of in 5 week-old rats, but the increasing rate of that was lower in 12 week-old rats. Hepatic alcohol dehydrogenase activity was also higher in 12 week-old rats than in 5 week-old rats whereas the increasing rate of that was higher in 5 week-old than those in 12 week-old rats by the xylene treatment. Furthermore, the hepatic aldehyde dehydrogenase activities were no differences between the 5 and 12 week-old rats both in the control and xylene-treated group. In conclusion, age may influences upon the hepatotoxicity with xylene and it may be responsible for xylene metabolism in rats.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.34-48
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• 1985

In vitro effects of nitrofurantoin, an antimicrobial agent for acute and chronic urinary tract infection, on the lung microsomal lipid peroxidation and the generation of reactive oxygen radicals were investigated to elucidate the biochemical mechanisms of its in vivopulmonary toxicity. The interaction of nitrofurantoin with porcine lung microsome resulted in significant lipid peroxidation. In addition, nitrofurantoin stimulated the generation of reactive oxygen radicals, $O^{-}_{2}{\cdot},\;H_2O_2$ as well as a highly reactive secondary oxygen species, $OH{\cdot}$. The stimulation of lipid peroxidation was inhibited not only by superoxide dismutase and catalase, but also by hydroxyl radical scavengers, mannitol and thiourea. Neither singlet oxygen $({^1}O_{2})$ was detected during the incubation of microsome with nitrofurantoin, nor lipid peroxidation was inhibited by singlet oxygen scavengers. When incubated anaerobically under the nitrogen atmosphere, the ability of nitrofurantoin to stimulatle lipid peroxidation was abolished. It appears that NADPH-dependent metaboliam of nitrofurantoin in pulmonary microsome under aerobic condition is accompanied by the stimulation of lipid peroxidation through the mediation of reactive oxygen radicals, particularly hydroxyl radical. It is strongly suggested from these results that the stimulation of pulmonary microsomal lipid peroxidation by the reactive oxygen radical may be a in vivo mechanism of pulmonary toxicity caused by nitrofurantoin.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.512-519
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• 2018

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

• Nutrition Research and Practice
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• v.5 no.1
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• pp.20-27
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• 2011

We conducted this study to examine the effects of safflower seed granular tea containing physiologically active polyphenols on antioxidative activities and bone metabolism. Forty postmenopausal women ages 49 to 64-years were recruited from Daegu and Gyeongbuk and were randomly assigned to either a safflower tea supplement (Saf-tea) group (n=27) or a placebo group (n=13). The Saf-tea group received 20 g of safflower seed granule tea per day containing a 13% ethanol extract of defatted safflower seeds, whereas the placebo group received a similar type of tea that lacked the ethanol extract. No significant changes in nutrient intake for either the placebo or Saf-tea groups were observed before or after the study period, except vitamin A intake increased after 6 months in the Saf-tea group. Dietary phytoestrogen intakes were similar in the Saf-tea group (60.3 mg) and placebo group (52.5 mg). Significant increases in plasma genistein and enterolactone were observed in the Saf-tea group. After 6 months of supplementation, serum levels of antioxidant vitamins such as a-tocopherol and ascorbic acid increased significantly, and TBARS levels decreased in the Saf-tea group compared to the placebo group. Serum osteocalcin levels were reduced (P<0.05) in the Saf-tea group after 6 months, whereas serum osteocalcin did not change in the placebo group. Urinary deoxypyridinoline/creatinine excretion was not different between the two groups at baseline, and did not change in either group after 6 months. Bone mineral density decreased significantly in the placebo group (P<0.01) but not in the supplemented group. It was concluded that polyphenols (72 mg/day), including serotonin derivatives, in the Saf-tea had both antioxidant and potential bone protecting effects in postmenopausal women without liver toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.597-602
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• 1997

Cytochrome P450 2E1 (CYP2E1) is involved in the toxicity and carcinogenicity of a number of solvents and xenobiotics. Like the various types of oxidation pharmacogenetics, the activity of the enzyme shows a discernible interindividual and interethnic variation. However, no pharmacogenetic information on CYP2E1 polymorphism has been available from a Korean population. The aim of this study was to explore the pharmacogenetics of CYP2E1 polymorphism in a native Koreans after an oral 400 mg dose of chlorzoxazone administered to 128 subjects. Urine samples were collected during the subsequent 8-hour period and urinary concentrations of chlorzoxazone and 6-hydroxychlorzoxazone were determined by a high performance liquid chromatography with an ultraviolet detector. The limit of detection in the samples was found to be $0.5\;{\mu}g/ml$. The mean value of the 6-hydroxychlorzoxazone excreted in 8 hr urine expressed as the percentage was 48.2 13.8%. The frequency distribution of percentage of the administered dose excreted as the 6-hydroxy metabolite was unimodally distributed in the subjects studied. However, the values showed wide (7-fold) interindividual difference, ranged from 11.6% to 79.8% of the dose of chlorzoxazone. Thus, it was considered that the pharmacogenetic characteristics of CYP2E1 in a Korean population did not represent multimodal distribution in the 6-hydroxychlorzoxazone excreted in 8-hr urine expressed as the percentage. And the activity of the CYP2E1 in a Korean population seemed to be less compared with that of the Caucasian subjects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.sup1
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• pp.72-82
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• 2008

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism that results in accumulation of copper primarily in the liver, the brain and the cornea. Mutations in the WD gene, ATP7B cause failure of copper excretion from hepatocyte into bile and a defective synthesis of ceruloplasmin. More than 370 mutations are now recognized, scattering throughout the ATP7B gene. Since WD has protean clinical presentations, awareness of WD in clinical practice is important for the early diagnosis and prevention of accumulated copper toxicity. None of the laboratory parameters alone allows a definite diagnosis of WD. There are numerous pitfalls in the diagnosis of WD. Low serum ceruloplasmin concentrations, increased 24 hour urinary copper excretion, increased hepatic copper concentrations and the presence of Kayser-Fleischer rings in the cornea are major diagnostic points. A combination of any two of these 4 laboratory findings is strong support for a diagnosis of WD. Molecular methods are now being used to aid diagnosis. Molecular genetic testing has confirmed the diagnosis in individuals in whom the diagnosis is not clearly established biochemically and clinically. Siblings should be screened for WD once an index case has been diagnosed. Discrimination of heterozygotes from asymptomatic patients is essential to avoid inappropriate lifelong therapy for heterozygotes. Genetic testing, either by haplotype analysis or by mutation analysis, is the only reliable tool for differentiating heterozygote carriers from affected asymptomatic patients. Currently, genetic testing is of limited value in the primary diagnosis. However, genetic testing will soon play an essential role in diagnosing WD as rapid advancement of biomedical technology will allow more rapid, easier and less expensive mutation detection.

• Journal of Life Science
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• v.11 no.6
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• pp.543-553
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• 2001

Lead poisoning is currently one of the major public health problems in industrialized countries. Several chelating agents have been developed and used to treat the lead poisoning. It was recently proposed that garlic, having a large quantity of S-S compounds, may react readily with lead, producing various sulfur componds, and thus provide curative and protective effects on the lead toxicity. The present study was undertaken to evaluate this possibility in experimental animals. The garlic treatment on rats pre-exposed to lead significantly enhanced urinary excretion of lead at a garlic dose of 500 mg/kg and decreased the bloon level of lead at both 250 and 500 mg/kg doses. The administration of grilic 500mg/kg along with lead significantly alleviated the renal histological alterations induced by lead. These results suggest that garilic has a curative as well as a protective effect against lead poisoning , thus it may act as a chelator of lead.

• Journal of Environmental Health Sciences
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• v.27 no.2
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• pp.10-16
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• 2001

To evaluate an effect of circadian variation on the xylene metabolizing enzyme activities, 50% m-xylene in olive oil(0.25 $m\ell$/100g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Then animals were sacrigiced at 8hr after last injection of m-xylene. Hepatic microsomal cytochrome p450 contents were more increased both in control and xylene treated rats of night phase than those of day phase. But the activity of hepatic alcohol dehydrogenase(ADH) in control of night phase showed the similar value with that in those of day phase and xylene treated rats of day phase showed an increasing tendency of hepatic ADH activity as those of night phase showing similar activity. Furthermore, control rats of night phase than those of day phase. And by xylene treatment, enzyme activities of rats of day phase were higher tendency in rats of control but those of night phase were somewhat inhibited. Besides, xylene-treated animals of night phase showed increasing tendency of urinary methylhippuric acid concentration compared with those of day phase. On the other hand, liver weight per body weight(%), hepatic lipid peroxide content and serum xanthine oxidase activity were higher in night phase. And the activities of hepatic oxygen free radical metabolizing enzymes such as xanthine oxidase, gluthathione S-transferase, and xylene-treated rats of night phase than those of day phase. In conclusion, it can be hypothesized on the basis of the results that the accumulation rate of m-xylene intermediate metabolite, i.e. m-methylbenzaldehyde in liver tissus may be higher in night phase than in day phase and it may be responsible for higher liver toxicity in bight phase than in day phase.

• Natural Product Sciences
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• v.25 no.3
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• pp.200-207
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• 2019

Albizzia julibrissin (AJ) is an herbal medicine that shows low toxicity, promotes promoting blood circulation and mitigates the inflammation and has mild side effects. Benign prostate hyperplasia (BPH) is one of the most common diseases that occurs in older males and often results in lower urinary tract symptoms. This study was conducted to evaluate the protective effect of AJ against BPH using LNCaP cells and Sprague Dawley rats treated with testosterone. Treatment with AJ extract reduced the expression of androgen receptor (AR) and prostate-specific antigen (PSA) in vitro. In vivo, rats were divided into 6 groups: 1 (Normal Control); 2 (Testosterone propionate (TP) alone); 3 (TP + finasteride); 4 (TP + AJ 10 mg/kg); 5 (TP + AJ 50 mg/kg); 6 (TP + AJ 300 mg/kg). The groups treated with AJ showed reduced the relative prostate weights and BPH-related proteins were altered, with decreased AR, PSA and proliferating cell nuclear antigen (PCNA) observed by western blot. Histopathological analysis revealed the therapeutic effect of AJ, with a decreased thickness of epithelial cells and reduced level of PCNA and $5{\alpha}$-reductase type 2. These results suggest that AJ extract could ameliorate testosterone-induced benign prostatic hyperplasia.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.29 no.2
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• pp.195-207
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• 2019

Objectives: This study was performed to confirm whether plasma lead can be used as a chronic biomarker for the biological monitoring of exposure to lead. Methods: Lead concentrations in 66 plasma samples from retired lead workers (G.M. 60.25 years, Median 61.00 years) and 42 plasma samples from the general population (G.M. 53.76 years, Median 56.50 years) were measured using ICP/Mass. Tibia, whole blood, hemoglobin, hematocrit, and blood zinc protophorphyrin (ZPP) concentrations and urinary ${\delta}$-aminolevulinic acid (${\delta}-ALA$) were measured for correlation analysis with plasma lead. Results: The geometric mean concentration of lead in plasma was $0.23{\mu}g/L$ for the retired lead workers and $0.10{\mu}g/L$ for the general population sample. A simple correlation analysis of biomarkers showed that plasma lead concentration among the retired lead workers was highly correlated with lead concentration in the tibia and with blood lead concentration, and the plasma lead concentration among the general population correlated with ZPP concentration in the blood. The lead concentration in the tibia and the lead concentration in the whole blood increased with length of working period. As the period in the lead workplace increased, the ratio of lead in plasma to lead concentration in whole blood decreased. Conclusion: This study confirmed the possibility of a chronic biomarker of lead concentration in blood plasma as a biomarker. In the future, comparative studies with specific indicators will lead to more fruitful results.