Protective Effects of Propofol against Methamphetamine-Induced Neurotoxicity

Context: Methamphetamine (METH) is widely abused in worldwide. METH use could damage the dopaminergic system and induce neurotoxicity via oxidative stress and mitochondrial dysfunction. Propofol, a sedative-hypnotic agent, is known for its antioxidant properties. In this study, we used propofol for attenuating of METH-induced neurotoxicity in rats. Subjects and Methods: We used Wistar rats that the groups (six rats each group) were as follows: Control, METH (5 mg/kg IP), and propofol (5, 10 and 20 mg/kg, IP) was administered 30 min before METH. After 24 h, animals were killed, brain tissue was separated and the mitochondrial fraction was isolated, and oxidative stress markers were measured. Results: Our results showed that METH significantly increased oxidative stress markers such as lipid peroxidation, reactive oxygen species formation and glutathione oxidation in the brain, and isolated mitochondria. Propofol significantly inhibited METH-induced oxidative stress in the brain and isolated mitochondria. Mitochondrial function decreased dramatically after METH administration that propofol pretreatment significantly improved mitochondrial function. Mitochondrial swelling and catalase activity also increased after METH exposure but was significantly decreased with propofol pretreatment. Conclusions: These results suggest that propofol prevented METH-induced oxidative stress and mitochondrial dysfunction and subsequently METH-induced neurotoxicity. Therefore, the effectiveness of this antioxidant should be evaluated for the treatment of METH toxicity and neurodegenerative disease.