Protective effects of naringenin against methamphetamine-induced cell death in dopaminergic SH-SY5Y cells

<i>Background:</i> Methamphetamine is a psychoactive substance that competes with the dopamine transporter, disrupting its flow and storage. This can trigger oxidative stress, finally resulting in neural cell death. Due to the increasing prevalence of methamphetamine use, extensive research has been devoted to finding treatments that ameliorate its detrimental effects. Naringenin, a dietary flavonoid found in citrus fruits, has shown several neuroprotective and pharmacological properties.<i>Objectives:</i> This study was aimed to assess the protective effects of naringenin against methamphetamine-induced dopaminergic cell death.<i>Methods:</i> Before exposure to methamphetamine, human neuroblastomaSH-SY5Y cells were either pretreated or not treated (controls) with naringenin. Cell viability, level of oxidative stress markers, and expression of some genes involved in apoptosis and autophagy processes were then assessed using MTT, ROS, and MMP assays, and qRT-PCR and Western blotting techniques.<i>Results:</i> Naringenin pretreatment significantly enhanced cell viability following methamphetamine exposure (<i>p</i> < .01). It significantly decreased ROS levels (<i>p</i> < .001), preserved mitochondrial membrane potential, and moderated upregulation of apoptotic (<i>CytC</i>, <i>Casp3</i>, and <i>Bax</i>) and autophagic genes (<i>Beclin</i>-1, and <i>LC-3</i>) and down-regulation of <i>Bcl-2</i> as an anti-apoptotic gene. Similar naringenin-mediated patterns were observed for cytochrome C and caspase 3 proteins.<i>Conclusion:</i> Naringenin administration can be considered for treating the neurotoxic effects of methamphetamine.