Neuroprotective effects of hydrogen sulfide on sodium azide-induced oxidative stress in PC12 cells

Alzheimer's disease (AD) is the most common neurodegenerative disorder, responsible for >50% of all dementia cases. Sodium azide (NaN(3)) inhibits cytochrome oxidase by irreversibly binding to the heme cofactor and selectively reducing the complex IV activity, which is present in post-mortem AD brains. Previous data demonstrated that hydrogen sulfide (H(2)S), the third endogenous gaseous mediator, exerted protective effects against neuronal damage. Therefore, it was hypothesized that H(2)S may be able to scavenge excess reactive oxygen species (ROS), thereby protecting against oxidative stress and cell death. In the present study, it was observed that cell viability decreased in a concentration-dependent manner 12 h after NaN(3) treatment (20, 30 and 50 mmol/l). A decrease in cell viability (to 51±3%) was observed 12 h after treatment with 30 mM NaN(3). NaN(3) treatment also led to decreased mitochondrial membrane potential, increased lipid peroxidation (excessive production of malondialdehyde), and increased the protein expression levels of caspase-3. Pretreatment with H(2)S (200 μmol/l) attenuated NaN(3)-mediated apoptosis, and the anti-apoptotic action of H(2)S was partially dependent on suppressing the production of ROS. The findings of the present study suggested that H(2)S exerted a neuroprotective effect against NaN(3)-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis. Therefore, the findings of the present study suggest there may be a promising future for H(2)S-based preventions and therapies for neuronal damage following exposure to NaN(3).