Effect and Mechanism of Pyridoxine in Alleviating Cisplatin-induced Acute Nephrotoxicity
OBJECTIVE To explore whether pyridoxine can protect acute kidney injury caused by cisplatin and to analyze its specific mechanism.METHODS After establishing an in vitro model of cisplatin-induced damage in HK-2 cells,different concentrations of pyridoxine were administered and cell survival was detected using SRB,the expression of apoptosis-related and antioxidant proteins were detected by Western blotting,and the activity of reactive oxygen species(ROS)and superoxide dismutase(SOD)were detected by kits.A cisplatin-induced mouse kidney injury model was further established,and the serum urea nitrogen level was detected after the administration of 40 mg·kg1pyridoxine treatment,the results of hematoxylin-eosin staining in renal tissue were analyzed,and the expression of NRF2 was detected by Western blotting.RESULTS Pyridoxine could protect kidney injury caused by cisplatin in HK-2 cells and mouse in vivo.In HK-2 cells,pyridoxine down-regulated ROS level,up-regulated SOD enzyme activity,and up-regulated the expression of NRF2 and its downstream antioxidant-related gene HO-1.Pyridoxine significantly reduced the level of serum urea nitrogen,repaired kidney tissue damage,and up-regulated the expression of NRF2 in kidney injury mice.CONCLUSION Pyridoxine protects against cisplatin-induced kidney injury through enhancing the level of anti-oxidative stress.