Akr7a5, an enzyme belonging to the Aldo-keto reductase-7A (AKR7A) subfamily of the AKR superfamily, plays a crucial role in aldehyde and ketone detoxification by reducing them to corresponding alcohols [4]. It is involved in protecting cells from oxidative stress and reactive aldehyde toxicity, with potential implications in multiple biological processes and diseases such as neurodegenerative diseases and cancer [4]. Genetic models, like KO mouse models, are valuable for studying its functions.

In AKR7A5-knockout (KO) mice, single ethanol binge led to more severe inflammatory response, oxidative stress, apoptosis of endogenous pathways, abnormal lipids metabolism and disordered coagulation in the liver compared to wild-type mice given alcohol [1]. This indicates that Akr7a5 deficiency exacerbates acute alcohol-induced liver injury. In vitro studies with transgenic mammalian cell lines expressing Akr7a5 showed that it protects cells from the cytotoxicity of H₂O₂, menadione, and lipid peroxidation-derived aldehydes, can lower cellular ROS levels, and maintain cellular glutathione homeostasis [2]. Also, in V79 cells, Akr7a5 expression conferred increased resistance to 4-hydroxynonenal (4-HNE) cytotoxicity, decreased the mutation rate in the presence of 4-HNE, and attenuated 4-HNE-induced caspase-3 activity, suggesting its role in protecting against 4-HNE-mediated apoptosis [3].

In conclusion, Akr7a5 is essential for protecting cells from oxidative stress and reactive aldehyde-induced damage. The KO mouse models have demonstrated its significance in preventing acute liver injury caused by alcohol, highlighting its potential importance in liver-related disease areas.