• 제목/요약/키워드: Zinc protoporphyrin

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Suppression of Lipopolysaccharide-Induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae

  • Ji, Seon Yeong;Cha, Hee-Jae;Molagoda, Ilandarage Menu Neelaka;Kim, Min Yeong;Kim, So Young;Hwangbo, Hyun;Lee, Hyesook;Kim, Gi-Young;Kim, Do-Hyung;Hyun, Jin Won;Kim, Heui-Soo;Kim, Suhkmann;Jin, Cheng-Yun;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • 제29권6호
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    • pp.685-696
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    • 2021
  • In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

축전지 제조업에서 입사 1년 미만 남자 사원들의 연 노출 지표치에 관한 연구 (A study on lead exposure indices of male workers exposed to lead less than 1 year in storage battery industries)

  • 황보영;김용배;리갑수;이성수;안규동;이병국;김정순
    • Journal of Preventive Medicine and Public Health
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    • 제29권4호
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    • pp.747-764
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    • 1996
  • This study intended to obtain an useful information for health management of lead exposed workers and determine biological monitoring interval in early period of exposure by measuring the lead exposure indices and work duration in all male workers (n=433 persons) exposed less than 1 year in 6 storage battery industries and in 49 males who are not exposed to lead as control. The examined variables were blood lead concentration (PBB), Zinc-protoporphyrin concentration (ZPP), Hemoglobin (HB) and personal history; also measured lead concentration in air (PBA) in the workplace. According to the geometric mean of lead concentration in the air, the factories were grouped into three categories: A; When it is below $0.05mg/m^3$, B; When it is between 0.05 and $0.10mg/m^3$, and C; When it is above $0.10mg/m^3$. The results obtained were as follows: 1. The means of blood lead concentration (PBB), ZPP concentration and hemoglobin(HB) in all male workers exposed to lead less than 1 year in storage battery industries were $29.5{\pm}12.4{\mu}g/100ml,\;52.9{\pm}30.0{\mu}g/100ml\;and\;15.2{\pm}1.1\;gm/100ml$. 2. The means of blood lead concentration (PBB), ZPP concentration and hemoglobin(HB) in control group were $5.8{\pm}1.6{\mu}g/100ml,\;30.8{\pm}12.7{\mu}g/100ml\;and\;15.7{\pm}1.6{\mu}g/100ml$, being much lower than that of study group exposed to lead. 3. The means of blood lead concentration and ZPP concentration among group A were $21.9{\pm}7.6{\mu}g/100,\;41.4{\pm}12.6{\mu}g/100ml$ ; those of group B were $29.8{\pm}11.6{\mu}g/100,\;52.6{\pm}27.9{\mu}g/100ml$ ; those of group C were $37.2{\pm}13.5{\mu}g/100,\;66.3{\pm}40.7{\mu}g/100ml$. Significant differences were found among three factory group(P<0.01) that was classified by the geometric mean of lead concentration in the air, group A being the lowest. 4. The mean of blood lead concentration of workers who have different work duration (month) was as follows ; When the work duration was $1\sim2$ month, it was $24.1{\pm}12.4{\mu}g/100ml$, ; When the work duration was $3\sim4$ month, it was $29.2{\pm}13.4{\mu}g/100ml$ ; and it was $28.9\sim34.5{\mu}g/100ml$ for the workers who had longer work duration than other. Significant differences were found among work duration group(P<0.05). 5. The mean of ZPP concentration of workers who have different work duration (month) was as follows ; When the work duration was $1\sim2$ month, it was $40.6{\pm}18.0{\mu}g/100ml$, ; When the work duration was $3\sim4$ month, it was $53.4{\pm}38.4{\mu}g/100ml$ ; and it was $51.5\sim60.4{\mu}g/100ml$ for the workers who had longer work duration than other. Significant differences were found among work duration group(P<0.05). 6. Among total workers(433 person), 18.2% had PBB concentration higher than $40{\mu}g/100ml$ and 7.1% had ZPP concentration higher than $100{\mu}g/100ml$ ; In workers of factory group A, those were 0.9% and 0.0% ; In workers of factory group B, those were 17.1% and 6.9% ; In workers of factory group C, those were 39.4% and 15.4%. 7. The proportions of total workers(433 person) with blood lead concentration lower than $25{\mu}g/100ml$ and ZPP concentration lower than $50{\mu}g/100ml$ were 39.7% and 61.9%, respectively ; In workers of factory group A, those were 65.5% and 82.3% : In workers of factory group B, those were 36.1% and 60.2% ; In workers of factory group C, those were 19.2% and 43.3%. 8. Blood lead concentration (r=0.177, P<0.01), ZPP concentration (r=0.135, P<0.01), log ZPP (r=0.170, P<0.01) and hemoglobin (r=0.096, P<0.05) showed statistically significant correlation with work duration (month). ZPP concentration (r=0.612, P<0.01) and log ZPP (r=0.614, P<0.01) showed statistically significant correlation with blood lead concentration 9. The slopes of simple linear regression between work duration(month, independent variable) and blood lead concentration (dependent variable) in workplace with low air concentration of lead was less steeper than that of poor working condition with high geometric mean air concentration of lead. The study result indicates that new employees should be provided with biological monitoring including blood lead concentration test and education about personal hygiene and work place management within $3\sim4$ month.

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