Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway.
Environ Toxicol
; 38(7): 1628-1640, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-36988346
ABSTRACT
Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 µM) for 24 h. About 50 µM DAPT and 100 µg/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1ß. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.
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MEDLINE
Assunto principal:
Dietilexilftalato
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article