
-   The reduction of the aflatoxin B 1 (AFB 1) dialdehyde metabolite to its corresponding mono and dialcohols, which is catalyzed by aflatoxin B 1-aldehyde reductase, is greatly increased in livers of rats treated with numerous chemoprotective agents [PMID: 18416522]. The hepatocarcinogen aflatoxin is activated by P4503A4 to aflatoxin epoxide [PMID: 8261428], which undergoes hydrolysis and ring opening to form the dialdehyde. The AKR7A3 enzyme metabolizes aflatoxin dialdehyde to the mono- and dialcohols, preventing the dialdehyde from forming Schiff bases with proteins.
-   AKR7A3 affected the metastasis, autophagy, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC) by regulating PHGDH and the autophagy pathway [PMID: 36951402].
-   AKR7A3 suppresses tumorigenicity and chemoresistance in hepatocellular carcinoma through attenuation of ERK, c-Jun and NF-kB signaling pathways [PMID: 29137357].

## Summary

The Akr7a3 gene encodes an enzyme crucial in the liver's detoxification process [CS: 8]. It specifically addresses the threat posed by aflatoxin B1 (AFB1), a harmful hepatocarcinogen [CS: 10]. AFB1 is activated by P4503A4 to a more dangerous epoxide form [CS: 8], which further converts into a dialdehyde [CS: 7]. Akr7a3's role is to metabolize this dialdehyde into less reactive mono- and dialcohols [CS: 8]. This action is vital as it prevents the dialdehyde from binding with proteins to form Schiff bases, a process that can cause significant cellular damage and lead to carcinogenesis [CS: 9].

In liver diseases like hepatocellular carcinoma (HCC), the dysregulation of Akr7a3 is linked to increased liver damage and a higher risk of cancer [CS: 7]. When Akr7a3 expression is reduced, the liver's capacity to detoxify AFB1 is impaired, resulting in the accumulation of more harmful substances [CS: 6]. This reduction in Akr7a3 expression weakens the liver's protective mechanisms, particularly its role in suppressing tumorigenicity and chemoresistance, by affecting critical signaling pathways like ERK, c-Jun, and NF-kB [CS: 5]. This weakened state makes the liver more vulnerable to disease and less capable of combating the toxic effects of substances like AFB1 [CS: 6].
