Human aldo-keto reductase-7A3 protects LO2 cells against APAP-induced oxidative stress and cell death

Human aldo-keto reductase-7A (AKR7A3) also referred to as aflatoxin aldehyde reductases (AFAR) is NADPH dependent oxidoreductases. Previous studies have shown that AKR7A3 is capable of detoxifying liver toxin aflatoxin B1 to less toxic alcohol. This study was carried out to investigate whether AKR7A3 is involved in the detoxification of acetaminophen (APAP), a commonly used drug for the fever and pain but is capable of inducing hepatic toxicity.
Liver LO2 cells were transiently transfected with AKR7A3 over-expressing plasmid pFLAG-AKR7A3 or the control vector pFLAG-CMV. 24 hours after the transfection, cells were treated with APAP at 4 mM for 24 or 48 hours. Following the APAP treatment, cell viability (MTT assay), intracellular ROS, GSH, and mRNA of antioxidant and dehydrogenase enzymes were determined.
Results following APAP treatment, LO2 cells showed significant dose- and time-dependent increased in ROS production, decreased in GSH level and cell viability. Interestingly, APAP treatment significantly induced AKR7A3 mRNA and protein expression, suggesting AKR7A3 might be involved in the protection against APAP insults. Indeed, LO2 cells overexpressing AKR7A3 showed significantly attenuated ROS production and partially recovered GSH level, and mRNA induction of NADPH producing enzymes as well as antioxidant defense.
Conclusions this results demonstrate that AKR7A3 contributes to protection against APAP-induced hepatocellular toxicity that probably is achieved in part through enhancing the anti-oxidative defensive mechanisms and induction of NADPH producing enzymes therefore, maintained the GSH levels.