
-   APAP, NAPQI, and NRF2: Akr7a might be transcriptionally regulated by oxidative stress-responsive transcription factor Nrf2, a protein highly responsive to acetaminophen (APAP) or its intermediate metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). In response to APAP or NAPQI exposure, Akr7a3 mRNA and protein were significantly up-regulated in human HepG2 and LO2 cells. Increased AKR7A3 in HepG2 cells was associated with the up-regulation of oxidative stress-related enzymes to enhance cellular antioxidant defense, which appeared to contribute to protection against APAP-induced toxicity [PMID: 21688283]. Knockdown of Nrf2 in HepG2 cells led to a reduction of AKR7A3 mRNA and AKR7A3 protein and increased sensitivity to acetaminophen-induced cytotoxicity [PMID: 21688283].
-   Keap1: AKR7A3 expression is regulated by the Keap1/Nrf2 system [PMID: 27806574].
-   Quercetin: Quercetin dose-dependently increased the mRNA expression of Akr7a3. It is apparent that quercetin increases the mRNA expression of Akr involved in drug metabolism in an isoenzyme-specific manner in rat liver [PMID: 19191009].
