Akr7a5, a member of the Aldo-keto reductase-7A (AKR7A) subfamily, is involved in the detoxification of aldehydes and ketones by reducing them to corresponding alcohols [4]. It has both aldehyde detoxification and antioxidant effects, and may participate in metabolic pathways related to fatty acid metabolism, reactive oxygen species (ROS) regulation, and coagulation [1]. Genetic models, such as knockout mice, are valuable for studying its functions.

In AKR7A5 -/- mice (KO), compared to wild-type mice with alcohol treatment, the KO + alcohol group showed abnormal liver function, disordered hepatic cord, severe congestion, oxidative stress, DNA damage, and abnormal apoptosis-related protein expressions [1]. This indicates that Akr7a5 deficiency, combined with single ethanol binge, leads to more severe inflammatory response, oxidative stress, apoptosis of endogenous pathways, abnormal lipids metabolism, and disordered coagulation in the mouse liver [1].

In conclusion, Akr7a5 plays a crucial role in protecting cells from oxidative stress and aldehyde-induced toxicity [2,3]. The AKR7A5 KO mouse model has revealed its significance in preventing acute liver injury, especially in the context of alcohol-induced damage, highlighting its potential as a target for understanding and treating alcohol-related liver diseases [1].

References:

1. Shi, Hui, Xu, Wenda, Liu, Qingling, Dong, Silin, Zhao, Zhenjun. . AKR7A5 knockout promote acute liver injury by inducing inflammatory response, oxidative stress and apoptosis in mice. In Journal of cellular and molecular medicine, 28, e70129. doi:10.1111/jcmm.70129. https://pubmed.ncbi.nlm.nih.gov/39365156/

2. Li, Dan, Ellis, Elizabeth M. 2014. Aldo-keto reductase 7A5 (AKR7A5) attenuates oxidative stress and reactive aldehyde toxicity in V79-4 cells. In Toxicology in vitro : an international journal published in association with BIBRA, 28, 707-14. doi:10.1016/j.tiv.2014.02.010. https://pubmed.ncbi.nlm.nih.gov/24590062/

3. Li, Dan, Hinshelwood, Alison, Gardner, Rachel, McGarvie, Gail, Ellis, Elizabeth M. 2006. Mouse aldo-keto reductase AKR7A5 protects V79 cells against 4-hydroxynonenal-induced apoptosis. In Toxicology, 226, 172-80. doi:. https://pubmed.ncbi.nlm.nih.gov/16919859/

4. Zhao, Mengli, Chen, Jiajin, Chen, Hongyu, Zhang, Jingdong, Li, Dan. 2024. Aldo-keto reductases 7A subfamily: A mini review. In Chemico-biological interactions, 391, 110896. doi:10.1016/j.cbi.2024.110896. https://pubmed.ncbi.nlm.nih.gov/38301882/