Fight Back: Adaptive Responses to Toxicant Exposure

摘要: The popularity of barbiturate sedatives in bygone days helped physicians discover an unusual property these medicines: on repeated use, patients experienced a dramatic loss effectiveness, with higher and doses required to elicit the original drug response. This capacity for physical tolerance alerted researchers phenomenon enzyme induction: upon sustained exposure, liver other tissues simultaneously boost expression enzymes that convert xenobiotics water-soluble metabolites membrane transporters expel via bile or urine. These outcomes reflect actions xenosensors – bifunctional proteins detect ingested then activate broad transcriptional responses facilitate their clearance from body. While such adaptive changes protect body by altering toxicokinetic fate xenobiotics, also occur at subcellular level against cell-damaging reactive metabolites. Upon detecting cell protein damage caused electrophiles, cells mount strong suppress toxicodynamic properties number pathways including heat shock response, antioxidant unfolded response NFkB pathway.