Marzieh Bavari1, Mohammad Reza Tabandeh1, Hosein Najafzadeh Varzi2, Somayeh Bahramzadeh3. 1. a Department of Biochemistry and Molecular Biology and. 2. b Department of Pharmacology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz , Ahvaz , Iran , and. 3. c Faculty of Medicine , Cellular and Molecular Research Center (CMRC), Ahvaz Jundishapour University of Medical Sciences (AJUMS) , Ahvaz , Iran.
Abstract
CONTEXT: Caffeine is the most widely consumed nervous stimulant that induces oxidative-mediated apoptosis and cell cycle arrest in neural cells. Due to low toxicity, high accumulation in neural cells, reduction of the free fatty acids and antioxidant property, l-carnitine (LC) is an interesting compound to be used in vivo against several neuropathies. OBJECTIVES: This study was conducted to evaluate the protective effect of LC against caffeine-induced cytotoxicity in SH-SY5Y neuroblastoma cell line. MATERIALS AND METHODS: SH-SY5Y neuroblastoma cells were incubated with cytotoxic doses of caffeine (5 and 10 mM) in the presence or absence of LC (1 and 5 mM) for duration of 18-24 h. The antioxidant factors, DNA fragmentation and cytotoxic markers were assessed in treated cells. RESULTS: Our results showed that 5 mM LC for 18 h protected SH-SY5Y cells against cytotoxicity induced by both doses of caffeine. This protection was related to the inhibition of reactive oxygen species generation, the increase in the superoxide dismutase and catalase activities and glutathione content and the prevention of lipid peroxidation in cultured SH-SY5Y cells. Apoptosis markers such as DNA fragmentation and caspase-3 activity were also inhibited by 5 mM LC in caffeine-treated cells. DISCUSSION AND CONCLUSION: Our results suggest that LC could protect SH-SY5Y cells from caffeine-induced injury through the inhibition of oxidative damage, mitochondria dysfunction and inhibition of cell apoptosis. Our results indicate that LC therapy may be a valuable approach for the suppression of oxidative stress-related apoptosis in various neural diseases.
CONTEXT: Caffeine is the most widely consumed nervous stimulant that induces oxidative-mediated apoptosis and cell cycle arrest in neural cells. Due to low toxicity, high accumulation in neural cells, reduction of the free fatty acids and antioxidant property, l-carnitine (LC) is an interesting compound to be used in vivo against several neuropathies. OBJECTIVES: This study was conducted to evaluate the protective effect of LC against caffeine-induced cytotoxicity in SH-SY5Y neuroblastoma cell line. MATERIALS AND METHODS:SH-SY5Y neuroblastoma cells were incubated with cytotoxic doses of caffeine (5 and 10 mM) in the presence or absence of LC (1 and 5 mM) for duration of 18-24 h. The antioxidant factors, DNA fragmentation and cytotoxic markers were assessed in treated cells. RESULTS: Our results showed that 5 mM LC for 18 h protected SH-SY5Y cells against cytotoxicity induced by both doses of caffeine. This protection was related to the inhibition of reactive oxygen species generation, the increase in the superoxide dismutase and catalase activities and glutathione content and the prevention of lipid peroxidation in cultured SH-SY5Y cells. Apoptosis markers such as DNA fragmentation and caspase-3 activity were also inhibited by 5 mM LC in caffeine-treated cells. DISCUSSION AND CONCLUSION: Our results suggest that LC could protect SH-SY5Y cells from caffeine-induced injury through the inhibition of oxidative damage, mitochondria dysfunction and inhibition of cell apoptosis. Our results indicate that LC therapy may be a valuable approach for the suppression of oxidative stress-related apoptosis in various neural diseases.