The uncontrolled production of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) in CILI, AILI and DILI models was also suppressed by PNP80b-2.
The canonical pathway comparison showed that VOAAF and DILI both worked on aryl hydrocarbon receptor (AHR), lipopolysaccharide (LPS)/interleukin 1 (IL-1) mediated inhibition of retinoid X receptor (RXR) function, pregnane X receptor (PXR)/RXR activation, xenobiotic metabolism, peroxisome proliferator-activated receptor (PPAR), hepatic cholestasis, farnesoid X receptor (FXR)/RXR activation, and glucocorticoid receptor.
We investigated 30 clinical drugs with different safety profiles with regard to DILI and found that the total sum score of gene expression levels of S100A8, S100A9, RAGE, NALP3 and IL-1β mRNA in HL-60 or K562 cells incubated with HLM, could identify drugs at high risk for hepatotoxicity.
It seems that treatment of acute and chronic infections and/or inflammations with, for example, antibacterials not metabolized in the liver, and use of medications that decrease proinflammatory cytokine levels (eg, pentoxifylline, a TNF-alpha synthesis inhibitor, directed against TNF-alpha-induced priming of human neutrophils, immunotherapy with IL-4, IL-1 receptor antagonists or factors inducing IL-1ra, dietary supplementation with long-chain n-3 fatty acids, and other antioxidant agents) may perhaps, in some cases, be helpful in the prevention and management of drug-induced hepatotoxicity.