TDF-induced receptors (AhR2 and PXR) changed many genes involved in steroid metabolism, and subsequent disruptions in steroid homeostasis, which might be the key biological pathway in TDF reproductive toxicity.
Major xenobiotic receptors, including PXR, CAR and AhR, predominantly localized in the liver and intestines, have been documented as important xenobiotic sensors mediating the transcription of drug-metabolizing enzymes and transporters associated with the metabolism and clearance of oxazaphosphorines. 3.1....
SIGNALING PATHWAYHUMANMACROPHAGESINFLAMMATORY RESPONSESIntroduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for regulating expression of several important drug-detoxifying proteins. Besides drug metabolism pathways, cytokines have been recently recognized as...
The term “xenobiotic” refers to any foreign substance or exogenous chemical appearing in a biological system that is extrinsic to the normal metabolism of that system. The “xeno” in xenobiotic comes from the Greek word “ξένος” (xenos) meaning foreigner or stranger, while “biotic...
Whereas persistent activation of the AHR signaling pathway is responsible for the spectrum of adverse effects produced by metabolically stable AHR ligands such as TCDD, activation of AHR signaling by TCDD at nontoxic concentrations or by less persistent AHR agonists has also been shown to have some ...
“neuroinflammatory” processes. During different processes of cellular aerobic metabolism such as mitochondrialoxidative phosphorylation,reactive oxygen species(ROS) like superoxide (O2•−), hydrogen peroxide (H2O2),hydroxyl radical(•OH), andperoxynitrite(ONOO—) are generated. Excess production of ...
Interestingly, fecal tryptophan levels are elevated in patients with Crohn’s disease, suggesting perhaps that tryptophan metabolism is blunted in the microbiota of these patients (Jansson et al., 2009). In keeping with this notion of reduced tryptophan metabolism, indoxyl sulfate (product of indole...
Enhanced FXR signaling may also promote fatty acid and carbohydrate metabolism68,69 in the absence of PXR and CAR. T-UDCA was down-regulated in feces of PXR-null and CAR-null mice, and it is known to be a TGR-5 agonist with anti-inflammatory effects70. Therefore, the decrease in T-...