여름정기학술대회
2022여름초록
발표자 및 발표 내용
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발표구분 |
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포스터발표 |
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Brief Oral Presentation 발표신청 |
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국가 |
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공동저자
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접수자
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Di-(2-Ethylhexyl)
phthalate (DEHP) is a ubiquitous environmental endocrine disruptor that
adversely affects homeostasis, reproduction, and developmental processes. DEHP
can be inevitably penetrated through the air, food, cosmetics, and plastic
devices. After absorption, it shortly converts to Mono-2-ethylhexyl phthalate
(MEHP) which has higher toxicity. The previous studies to date clarify the
damage derived from exposure to DEHP and its metabolites have been shown to
differ by sex and age, emphasizing the importance of understanding the
toxicokinetic and metabolomic activity of these chemicals. However, the
underlying mechanisms are still unclear.
In
this study, we treated 10mg/kg of DEHP by intravenous injection or oral
administration to adult male and female rats (9 weeks) and young female rats (5
weeks) and obtained plasma, urine, and 6 tissues (lung, kidney, liver,
testicle, womb, and ovary) for observing toxicokinetic processes of the major
metabolites of DEHP: MEHP, mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP),
mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP). In addition, an untargeted
metabolomics analysis was performed using urine collected at five different
times (0, 4h, 8h, 12h, and 24h) to present differentiated metabolic pathways by
exposure to DEHP.
For the determination of the significant variables, multivariate statistical
analysis using ANOVA-simultaneous component analysis (ASCA) and partial least
squares-discriminant analysis (PLS-DA) were used, and we found that metabolic
profiles were significantly different in sex and age. From the important
metabolites that induced the difference on sex and age over time, it can be
suggested that steroid hormone biosynthesis, taurine and hypotaurine
metabolism, linoleic acid metabolism and primary bile acid biosynthesis were
affected by the absorption of DEHP. Overall, this study systematically
describes the comprehensive mechanism of DEHP exposure to sex and age and
highlights the power of toxicokinetic model design and appropriate multivariate
statistical analysis using ASCA combined with PLS-DA in the discovery of key
metabolomics pathway.
This study can provide the scientific reference for understanding sex and age-dependent toxicokinetics and metabolic pathways following exposure to DEHP.
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