6-Formyl-5-isopropyl-3-hydroxymethyl- 7-methyl-1H-indene mitigates methamphetamine-induced photoreceptor cell toxicity through inhibiting oxidative stress.

Abstract

As an extremely addictive psychostimulant drug and an illicit dopaminergic neurotoxin, methamphetamine (METH) conducts to enhance satisfaction, feelings of alertness through influencing monoamine neurotransmitter systems. Long-lasting exposure to METH causes psychosis and increases the risk of neurodegeneration. 6-Formyl-5-isopropyl-3-hydroxymethyl-7-methyl-1H-indene (FIHMI) is a novel compound with potent antioxidant properties. This study was to investigate whether FIHMI could mitigate METH-induced photoreceptor cell toxicity. METH-caused cell toxicity was established in 661W cells and protective effects of FIHMI at different concentrations (1-10 µM) was examined. FIHMI significantly attenuated the METH-caused cell damage in 661W cells, evidenced by increasing cell viability and mitochondrial membrane potential, decreasing cytochrome c release and DNA fragmentation, inhibiting activities of caspase 3/9, and changing expression of apoptosis-related protein. Furthermore, FIHMI treatment decreased mRNA expression of Beclin-1 and LC3B protein expression in METH-induced 661W cells suggesting autophagy is reduced. FIHMI decreased the oxidative stress through increasing protein expression of nuclear factor (erythroid-derived 2)-like 2. These data demonstrated FIHMI could inhibit oxidative stress, which may also play an essential role in the regulation of METH-triggered apoptotic response, providing the scientific rational to develop FIHMI as the therapeutic agent to alleviate METH-induced photoreceptor cell toxicity.