Akr7a5, belonging to the Aldo-keto reductase-7A (AKR7A) subfamily of the AKR superfamily, functions in the detoxification of aldehydes and ketones by reducing them to corresponding alcohols [4]. It is associated with multiple pathways such as those related to oxidative stress response and lipid peroxidation-derived aldehyde metabolism, playing a significant role in maintaining cellular homeostasis. Genetic models, like the KO mouse model, are valuable for studying its functions.

In a study using AKR7A5 -/- mice (KO), single ethanol binge in these mice 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 with alcohol treatment. This indicates that Akr7a5 absence exacerbates acute alcohol-induced liver injury [1]. In cell-based studies, over-expressing Akr7a5 in V79-4 cells protected against the cytotoxicity of H2O2, menadione and several lipid peroxidation-derived aldehydes, and also helped maintain cellular glutathione homeostasis and cope with ROS accumulation [2]. Mouse V79 cells expressing Akr7a5 showed decreased 4-hydroxynonenal-induced caspase-3 activity, suggesting attenuation of apoptosis [3]. Depletion of Akr7a5 in cultured AML12 cells greatly increased acetaminophen-induced hepatotoxicity [5].

In conclusion, Akr7a5 is crucial for protecting cells from oxidative stress and reactive aldehyde toxicity, as demonstrated through model-based research. Its absence in KO mouse models exacerbates liver injury in the context of alcohol-induced and acetaminophen-induced stress, highlighting its importance in maintaining liver health and potentially in treating liver-related diseases.