• 한국산업보건학회지
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• 제11권2호
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• pp.111-117
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• 2001

A cross-sectional study was performed to evaluate associations between lead biomarkers, lead-related symptoms, and ${\delta}$-aminolevulinic acid dehydratase (ALAD) genotype among 598 lead workers and 144 control office workers in storage battery industries, secondary smelting and litharge making industries. Lead inhibits the second enzymes, ALAD, in the heme synthesis pathway. ALAD gene, which codes for one of three isozymic proteins (termed ALAD1-1, ALAD1-2, and ALAD2-2), seems to modify the toxicokinetics of lead. The result as follows; The percents of total workers whose genotype of ALAD1-1 and ALAD1-2 were 88.4% and 11.6%, respectively. The zinc protoporphyrin in blood (ZPP) and ${\delta}$-aminolevulinic acid in urine (ALAU) of lead workers with ALAD1-2 were significantly lower than those of lead workers with ALAD1-1, but there were no significant difference between two genotype for blood lead, age, and work duration. The proportion of ALAD1-2 genotype in control office workers was 13.2%. The proportions of ALAD1-2 genotype of lead workers were 14.0%(their mean air lead level below $0.024mg/m^3$), 10.4%($0.025-0.049mg/m^3$), 11.8%($0.050-0.099mg/m^3$), and 9.4%(above $0.100mg/m^3$), respectively. In the logistic analysis of 15 lead related symptoms, 'arthralgia'(S7) symptom of ALAD1-2 was significantly lower (OR=0.481; 95% CI=0.248-0.932) than that of ALAD1-1, but 'feeling of irritation'(S11) of ALAD1-2 was significantly higher(OR=1.636; 95% CI=1.035-2.586) than that of ALAD1-1 after controlling possible confounder (blood lead, work duration, smoking and drinking habit).

• 한국식품영양과학회지
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• 제40권11호
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• pp.1507-1511
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• 2011

본 연구에서는 LPS에 의해 활성화된 RAW264.7 대식세포에서의 NO 생성 및 iNOS와 HO-1 단백질 발현의 변화를 측정하여 개망초(Erigeron annuus L.) 꽃(EAF) methanol 추출물의 항염증 효과를 확인하였다. RAW264.7 대식세포에 LPS를 처리한 결과 NO의 함량이 11.48 ${\mu}m$ 수준으로 증가하였다. 그러나 EAF methanol 추출물(25, 50, 100, 200 ${\mu}g$/mL)을 처리하였을 때 NO의 함량이 12.82, 9.61, 6.83, 2.52 ${\mu}m$로 농도 의존적으로 감소하였다. 또한 EAF methanol 추출물은 NO의 생성에 관여하는 iNOS 단백질의 발현을 농도 의존적으로 저해하였으며 HO-1 단백질의 발현을 유도하였다. EAF methanol 추출물에 의한 HO-1 발현이 NO 생성에 미치는 영향에 대해 확인하기 위해 HO-1의 inhibitor인 ZnPP를 사용하였다. 실험결과 ZnPP를 처리하여 HO-1의 발현을 저해하였을 때 추출물에 의해 감소된 NO의 함량이 다시 증가되었다. 본 연구 결과, EAF methanol 추출물은 염증을 유발하는 중요 인자인 NO를 저해하였고, iNOS의 발현을 억제시켰으며 산화적 손상으로부터 세포 보호 방어 기작에 관여하는 HO-1의 발현 등 항염증에 우수한 효과를 보였으며 항염증 연구의 기초 자료로 활용될 것으로 예상된다.

• Journal of Preventive Medicine and Public Health
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• 제31권4호
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• pp.708-718
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• 1998

To investigate the effect of smoking and drinking habit on the health status in lead using industries, 2,785 male workers in lead using industries (7 storage battery industries, 7 secondary smelting and related industries, and 4 primary metal and other manufacturing industries) were selected for this study. This study was carried out as a part of periodic health examination. Selected study variables were zinc protoporphyrin in whole blood (ZPP), SGOT and SGPT for laboratory test. Questionnaire for lead related symptoms and smoking and drinking habit was provided to all the workers and filled up by themselves and reconfirmed by physician. The results obtained were as follows; 1. The overall smoking and drinking rate of study population were 69.8% and 73.6%, respectively. While the smoking and drinking rate of storage battery workers were 68.8% and 72.3%, those of secondary smelting industries and other industries were 66.0% & 66.4% and 74.6 & 80.3% respectively. 2. While the mean values of blood ZPP of lead exposed workers were significantly higher than other group, those of SGOT of storage battery workers were significant higher than other worker. But there were no differences of mean values of other variables. 3. Smoking habit did not affect on the mean value of blood ZPP of workers in special health examination group, but there were significant differences of blood ZPP and SGOT between drinker and non-drinker. 4. Symptom prevalence of lead exposure were higher in drinking and smoking group than non-drinking and non-smoking group. 5. In multiple regression analysis of the total lead related symptoms, blood ZPP, SGOT, and SGPT as dependent variable, respectively, and age, work duration, blood ZPP, pack year and amount of alcohol drinking as independent variables, work duration, pack year, amount of alcohol drinking, age contributed to total symptoms; and age, work duration, pack year contributed to blood ZPP; and age, amount of alcohol drinking, work duration contributed to SGOT; and pack year contributed to SGPT.

• 대한약침학회지
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• 제19권1호
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• pp.59-69
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• 2016

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

• 대한한의학방제학회지
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• 제25권1호
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• pp.1-10
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• 2017

Objectives : The fruit of Prunus mume Siebold & Zucc. has been used as an alternative medicine and functional food in Korea and Japan for preventive and therapeutic purposes. However, its molecular actions and mechanism on anti-inflammatory activity have not been clearly investigated. The aim of this study was to clarify the anti-inflammatory activity of the ethanol extract of P. mume fruit (EEPM) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, and sought to understand the associated molecular mechanisms. Methods : Cytotoxicity was assessed by an MTT assay. The amount of nitric oxide (NO) production was determined by nitrite assay. The mRNA expression of inducible nitric oxide synthase (iNOS) was analyzed by RT-PCR. In addition, expression levels of iNOS, nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein were detected by Western blotting. Results : Our data indicated that EEPM inhibited NO production in LPS-stimulated RAW264.7 cells in a concentration-dependent manner. At the mRNA and protein levels, EEPM suppressed LPS-induced iNOS expression. On the other hand, EEPM markedly enhanced HO-1 expression, which was associated with an induction and nuclear translocation of Nrf2. Moreover, the inhibitory effect of EEPM against LPS‑induced NO production was significantly enhanced by hemin, a HO-1 inducer; however, EEPM's effect on the production of NO was abolished by zinc protoporphyrin IX, a HO-1 inhibitor. Conclusion : The results suggest that EEPM can act as a suppressor agent on NO production through an activation of Nrf2/HO-1 signaling pathway, and may be a promising candidate for the treatment of inflammatory diseases.

• Journal of Preventive Medicine and Public Health
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• 제26권1호
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• pp.65-73
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• 1993

This study was carried out to evaluate the relationship between the biological lead exposure indices and air lead concentrations measured by personal air samplers. The 72 occupationally lead exposed workers were observed and the bioiogical lead Exposure indices chosen for this study were blood lead(PbB), urine lead(PbU), zinc protoporphyrin in whole blood(ZPP), $\delta$-aminolevulinic acid in urine(ALAU), $\delta$-aminolevulinic acid dehydratase activity (ALAD), coproporphyrin in urine(CPU) and hemoglobin(Hb). The workers were divided into four groups by air lead concentrations: Group I; under $0.05mg/m^3$, Group II; $0.05-0.10mg/m^3$, Group III; $0.10-0.15mg/m^3$ and Group IV; and over $0.15mg/m^3$. For evaluation the relationship between the biological lead exposure indices and air lead concentrations was used as correlation coefficients. The results obtained were as follows: 1. In Group I, II, III and IV, the mean value of PbB were $25.45{\pm}1.84{\mu}g/dl,\;27.87{\pm}3.53{\mu}g/dl,\;31.21{\pm}1.76{\mu}g/dl\;and\;47.02{\pm}13.96{\mu}g/dl$. Between Group IV and other groups showed statistically significant difference(p<0.05). 2. There was an increasing tendency of PbB, PbU, ALAU and ZPP according to the increase the mean air lead concentration, while ALAD has decreasing tendency. CPU and Hb did not show any constant tendency. 3. Correlation coefficients between PbB, PbU, ZPP, ALAU, ALAD, CPU, Hb and air lead concentration were 0.95, 0.83, 0.89, 0.72, -0.83, 0.51 and -0.45 respectively, and regression coefficient between PbB(Y) and PbA(X) was Y=126.8746X+16.9996(p<0.01).

• 대한본초학회지
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• 제20권3호
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• pp.29-41
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• 2005

Objectives : The use of natural products with therapeutic properties is as ancient as human civilisation and, for a long time, mineral, plant and animal products were the main sources of drugs. Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniceae) has been shown to possess anti-microbial and anti-tumoral properties. Heme oxygenase-1 (HO-1) is a stress response protein and is known to play a protective role against the oxidative injury. In this study, we examined whether catalposide could protect Neuro 2A cells, a kind of neuronal cell lines, from oxidative damage through the induction of HO-1 protein expression and HO activity. We also examined the effects of catalposide on the productions of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. Methods : HO-1 expression in Neuro 2A cells was measured by Western blotting analysis. NO and $TNF--{\alpha}$ produced by RAW 264.7 macrophage were measured by Griess reagent and enzyme-linked immunosorbent assay, respectively. Results : The treatment of the cells with catalposide resulted in dose- and time-dependent up-regulations of both HO-1 protein expression and HO activity. Catalposide protected the cells from hydrogen peroxide-induced cell death. The protective effect of catalposide on hydrogen peroxide-induced cell death was abrogated by zinc protoporphyrin IX, a HO inhibitor. Additional experiments revealed the involvement of CO in the cytoprotective effect of catalposide-induced HO-1. In addition, catalposide inhibited the productions of $TNF--{\alpha}$ and NO with significant decreases in mRNA levels of $TNF--{\alpha}$ and inducible NO synthase. Conclusions : Our results indicate that catalposide is a potent inducer of HO-1 and HO-1 induction is responsible for the catalposide-mediated cytoprotection against oxidative damage and that catalposide may have therapeutic potential in the control of inflammatory disorders.

• Journal of Preventive Medicine and Public Health
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• 제27권3호
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• pp.547-556
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• 1994

In order to identify the necessary information of biochemical Indices for renal effect of lead for the early detection in medical surveillance of lead worker, the reference values of urinary N-acetyl-$\beta$-D-glucosaminidase (NAG) activities were studied with 205 office workers in one industrial complex area who were not exposed to lead occupationally. While study variables selected for lead exposure were blood lead (PbB), blood zinc protoporphyrin(ZPP) and $\delta$-aminolevulinic acid (DALA) in urine, those for renal effect were urinary N-acetyl-$\beta$-D-glucosaminidase (NAG), blood urea nitrogen (BUN), serum creatinine(Cr), serum uric acid (Ua), and urinary total protein(U-TP). The results obtained were as follows: 1. The mean values of blood lead, ZPP and DALA in all subjects were $14.39{\pm}4.02{\mu}g/dl,\;21.61{\pm}8.00{\mu}g/dl,\;and\;2.73{\pm}0.90mg/l$ respectively. 2. The mean value of urinary NAG activities in all subjects was $3.51{\pm}2.01U/l$. The mean value of urinary NAG activities, which calculated from NAG activities divided by urinary creatinine concentration (CNAG), was $5.42{\pm}5.53U/g$ creatinine and log-arithmic normal distributed. 3. The reference value of urinary NAG activity was 12.06 U/g creatinine(95% CU=10.57-14.76 U/g creatinine). 4. Logarithmic CNAG(r=0.781 p<0.0l), U-TP(r=0.670 p<0.01) and ZPP(r=0.172 p<0.05) showed statistically significant correlation with CNAG.

• 생약학회지
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• 제43권1호
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• pp.39-45
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• 2012

Cirsium japonicum var. ussuriense has long been used in herbal medicine for the treatment of arthritis, dyspepsia, and bleeding in Korea. In the present study, we investigated anti-inflammatory effects of C. japonicum var. ussuriense against lipopolysaccharide(LPS)-induced activation in RAW264.7 cells by the expression of heme oxygenase (HO)-1. The 70% EtOH extract of the aerial parts of C. japonicum var. ussuriense (CJE), showed the potent anti-inflammatory effects on LPS-induced inflammation in RAW264.7 cells. The anti-inflammatory effect of CJE was demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Furthermore CJE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increased HO activity in RAW264.7 macrophages. The effects of CJE on LPS-induced NO and $PGE_2$ productions were partially reversed by an HO-1 inhibitor, tin protoporphyrin (SnPP). Therefore, it is suggested that CJE-induced HO-1 expression plays a role of the resulting anti-inflammatory effects in macrophages. These results suggest that CJE may be a promising candidate for the treatment of inflammatory diseases.

• Journal of Preventive Medicine and Public Health
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• 제19권2호
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• pp.167-176
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• 1986

For the purpose of determinating the normal values of some parameters relevant to lead exposure, a study was carried out from April 1 to June 30, 1986 on 258 healthy Korean adults who have had no apparant lead exposure. The lead indices subjected to this study were as follows; blood lead (PbB), hemoglobin (Hb), zinc protoporphyrin in blood (ZPP), delta-aminolevulinic acid dehydratase (ALAD) activity in blood, coproporphyrin in urine (CPU), delta-aminolevulinic acid in urine (ALAU). 1) The mean value of PbB was $17.17{\pm}7.87{\mu}g/100ml$, and there was no statistically significant difference by age & sex. The distribution of PbB fitted to the log-normal distribution ($x^2=7.38$, p>0.1). 2) The mean value of Hb in male ($15.17{\pm}1.56g/100ml$) was higher than in female ($13.22{\pm}1.51g/100ml$)(p<0.01). The distribution of Hb fitted to the normal distribution ($x^2=9.40$, p>0.1). 3) The mean value of ZPP was $32.61{\pm}8.78{\mu}g/100ml$, and there was no statistically significant difference by age & sex. The distribution of ZPP fitted to the normal distribution ($x^2=13.93$, p>0.05). The correlation of ZPP & ALAD (r=-0.229), CPU (r=0.183) was statistically significant respectively. 4) The mean value of ALAD was $30.20{\pm}10.96{\mu}mol$ ALA/min/L of R.B.C., and there was no statistically significant difference by age & sex. The distribution of ALAD activity did not fit to the normal distribution. The correlation between ALAD & PbB (r=-0.219) was statistically significant 5) The mean value of CPU was $36.10{\pm}24.54{\mu}g/L$, and there was no statistically significant difference by age & sex. The distribution of CPU did not fit to the normal distribution. The correlation between CPU & PbB (r=0.185), ZPP (r=0.183) was statistically signinificant respectively. 6) The mean value of ALAU was $1.94{\pm}0.96mg/L$, and there was no statistically significant difference by age & sex. The distribution of ALAU fitted to the normal distribution ($x^2=9.76$, p>0.1).