Effect of Carnosine on the Prevention of High- Dose Morphine-Induced Apoptosis of PC12 Cells

It has been reported that carnosine provide protection against various neurotoxic insults. In the previous study, we demonstrated that high dose morphine can induce apoptosis in PC12 cells possibly by the mitochondrial pathway through higher expression of Bax pro-apoptotic protein. The present study was designed to investigate the protective effect of carnosine on morphineinduced apoptotic death in PC12 cells. The activity of lactate dehydrogenase (LDH) and the levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), cell viability and DNA fragmentation were measured in morphine-treated PC12 cells with and without carnosine pre-treatment. Morphine caused concentrationdependent cell death and pretreatment with carnosine was associated with a marked diminution in DNA fragmentation, intracellular ROS and MDA levels. Carnosine also increased cell viability as measured by 3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) and LDH assays. These findings indicate that carnosine might be useful as potential agent to protect against morphine neurotoxicity.