Abstract

Diabetic neuropathy is one of the most common diabetic complications, associated with long time exposure to high glucose. Hyperglycemia induces the production of reactive oxygen species (ROS) and reactive nitrogen species contributing to neuronal damage. We have previously reported that HAMI 3379, a selective antagonist of CysLT₂ receptor, is involved in neuron injury after ischemia. In this study, we investigated the protective effect of HAMI 3379 against high glucose-induced cell injury in PC12 neural cells. The PC12 cells were pretreated with various concentrations of HAMI 3379 (0.001 ~ 10 µM) for 1 h and then co-treated with HAMI 3379 and D-glucose (100 mM) for 48 h. HAMI 3379 (0.001 ~ 10 µM) protected PC12 cells against high glucose toxicity, as determined by cell viability and apoptosis after the evaluation by Hoechst 33342 staining assay. In addition, the increased nitric oxide production and nitric oxide synthase (NOS) activity in the media induced by high glucose was significantly inhibited by HAMI 3379. These results demonstrate that HAMI 3379 protected PC12 cells against high glucose-induced neurotoxicity by inhibition of apoptosis, nitric oxide production and nitric oxide synthase activity, suggesting that CysLT₂ receptor may be a potential target for diabetic neuropathy, and its antagonist may play a crucial role in the treatment of diabetic neuropathy.

Key words: Cysteinyl leukotriene receptor, glucose, nitric oxide synthase, nitric oxide.