Lithocholic acid‐induced placental tumor necrosis factor‐α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy

Abstract

This study shows that the increase of TNF-α expression in placental trophoblasts is strongly associated with ICP pathology and is inducible by LCA in vitro, suggesting its potential value in the clinical prevention, diagnosis and treatment of ICP.

Galactosylated Poly(Ethyleneglycol)‐Lithocholic Acid Selectively Kills Hepatoma Cells, While Sparing Normal Liver Cells

“…The study further suggested that LCA‐induced apoptosis is proceeded through a mitochondrial/caspase‐9‐dependent pathway initiated by caspase‐8 . Most recent study suggested that LCA can directly induce syncytiotrophoblastic apoptosis in vitro, possibly via the TNF‐α pathway, with caspase‐3 activation . In this study, with the treatment of LPL, the catalytic activity of PARP and caspase‐3 in HepG2 was higher than in LO2, indicating that the mode of anti‐tumor effect of LPL is similar with the apoptosis induced by LCA via a caspase‐3‐dependent mechanism.…”

Bile acids and bilirubin effects on osteoblastic gene profile. Implications in the pathogenesis of osteoporosis in liver diseases

“…Previous studies observed LCA-induced apoptosis mediated by the nuclear receptor Nur77 expression in both human liver and colon cancer cells as well as in mouse hepatocytes [27]. LCA has also a pro-apoptotic effect in human colon adenocarcinoma cell lines [28], in human neuroblastoma cells [29] and in cultured 13 syncytiotrophoblast cells [30]. Finally, LCA induces apoptosis in human osteoblasts, increasing DNA fragmentation, caspase-3 activity and producing an up-regulation and a down-regulation of BAX and BCL2 respectively [24].…”

Transcriptome Profiling of Placenta through Pregnancy Reveals Dysregulation of Bile Acids Transport and Detoxification Function

“…Bile acids have also been reported to induce placental inflammation by activating G protein-coupled bile acid receptor 1( Gpbar1 )/ nuclear factor kappa B ( NF-κB ) [71], and placental damage, oxidative stress and apoptosis through tumor necrosis factor ( TNF , also known as TNFα ) and FXR [41,72]. The expression of these genes was not significantly different among G60, G90, and L0 (Tables S2 and S3), implying that the gestation stage-dependent increase of placental bile acids may be not sufficient to evoke placental inflammation and oxidative stress.…”