Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity

Oxidative stress-induced neuronal death plays a pivotal role in pathogenesis of neurodegenerative disorders. Recently, 7,8-dihydroxyflavone (7,8-DHF) has been shown to exert neuroprotective effects by acting as a selective tyrosine kinase receptor B (TrkB) agonist. In addition, the antioxidant action of 7,8-DHF may protect neuronal cells against oxidative injury. In the present study, we used PC12 cells, a cell line generally thought to lack TrkB, to investigate the effect of 7,8-DHF on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and the underlying mechanism. We found that 7,8-DHF effectively prevented cell death, apoptosis and mitochondrial dysfunction induced by 6-OHDA. In a cell free system, 7,8-DHF did not slow down extracellular auto-oxidation of 6-OHDA which may generate H2O2. However, We found that 7,8-DHF dramatically reduced cellular malondialdehyde content and phospho-histone H2A.X protein level. 7,8-DHF also elevated total superoxide dismutase activity in 6-OHDA-treated cells. These results indicate that 7,8-DHF might protect PC12 cells against 6-OHDA-induced cytotoxicity through its powerful antioxidant activity. By acting as a potent TrkB agonist and an antioxidant together with its easiness to pass across blood-brain barrier, 7,8-DHF may be developed into a promising candidate in treatment of neurodegenerative diseases.