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

Abstract

Abstract—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 morphine-induced 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 concentration-dependent 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, 5-dimethylthiazol-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.supplement [4]. It has been demonstrated that carnosine can scavenge reactive oxygen species (ROS) and exert neuroprotective effects through suppression of many biochemical changes such as protein oxidation, glycation, AGE formation and glutamatergic excitotoxicity [5]. These diverse pharmacological activities led us to speculate that treatment with carnosine may diminish neuronal damage triggered by high morphine concentrations. We used the rat pheochromocytoma cell line PC12, an in vitro model that is extensively used to study neurotoxicity [6]. In the previous study, we demonstrated that morphine can induce apoptosis in PC12 cells possibly by the mitochondrial pathway through higher expression of Bax pro-apoptotic protein [7]. In this study, we investigated for the first time the effect of carnosine in PC12 cells subjected to high concentrations of morphine.