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. 2022 Feb 10;10:826204. doi: 10.3389/fcell.2022.826204

FIGURE 3.

FIGURE 3

Drug-induced liver injury and Nrf2 drugs. Drugs metabolized by CYP are more likely to cause DILI. Reactive metabolites give rise to mitochondrial dysfunction, endoplasmic reticulum (ER) stress, or DNA damage. ROS and electrophiles activate Nrf2 to compound antioxidant proteins, alleviating DILI. For example, APAP can be metabolized by CYP to produce NAPQI, which detoxified by GSH at first. As APAP dosage increases, GSH exhausts and NAPQI accumulates, resulting in cytotoxicity. Reactive metabolites like ROS could stimulate Nrf2, initiating the transcription of target genes. CDDO and limonin could activate Nrf2 to compound NQO1, HO-1 and GCLC, which alleviate AILI. Omega-3 and AITC could also stimulate Nrf2 to compound HO-1 for alleviating AILI. But JNK phosphorylates Nrf2 to downregulate the transcriptional expression of cytoprotective genes in AILI. SFN, catalpol, Vitamin C and arctiin alleviate the liver damage induced by triptolide by activating Nrf2 to compound corresponding antioxidant proteins. AITC, allyl isothiocyanate; APAP, acetaminophen; CYP, cytochrome P450 proteins; DILI, drug-induced liver injury; GCLC, catalytic subunit of glutamate-cysteine ligase; GSH, reduced glutathione; HO-1, hemeoxygenase-1; JNK, c-Jun NH2 -terminal kinase; NAPQI, N-acetyl-1,4-benzoquinone imine; NQO1, quinone oxidoreductase 1; Nrf2, nuclear factor-erythroid 2-related factor 2; ROS, reactive oxygen species; SOD, superoxide dismutase; UGT1A6, UDP-glucuronosyltransferase 1A6.