Studies on human vascular smooth muscle cells treated with pro-inflammatory factors revealed that tannins, flavonoids, and carotenoids act on different cell signaling pathways and regulate genes involved in the inflammatory response [31]
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On the other hand, PERK induces translation initiation factor eIF2 phosphorylation ( NTZ has been reported to modulate UPR signaling, promoting antioxidant defenses, suppressing inflammatory cytokines, inhibiting PDI, and ultimately preventing cell injury ( Indeed, NTZ and its active circulating metabolite tizoxanide directly protect from stress-induced apoptosis and necroptosis to alleviate liver damage in acute-on-chronic liver failure rat model ( Apoe / mice ( In our attempt to scrutinize the hepatoprotective potential of NTZ and the possible implication of ER stress inhibition in our model of MTX-induced hepatotoxicity, we compared NTZ effects to a hepatoprotective NAC with documented ER stress inhibition and with a standard ER stress inhibitor (4-PBA) ( 5 Conclusion Collectively, it can be concluded that MTX-induced hepatotoxicity is mediated, at least in part, through ER stress, which was confirmed by the reversal of MTX toxicity upon administration of 4-PBA and NAC
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