Biphasic Neuroprotection from Depression-induced Oxidative Stress

Abstract

Objective: To create a two-hit cellular model of oxidative stress in depression and to assess the neuroprotective effects of fluoxetine and 808 nm photobiomodulation on cell survival, interleukin-6, glutathione and major depressive disorder depending on their doses.

Study Design: Experimental study
Place and Duration of Study: This study was conducted at the University of Babylon, Iraq from 15th January 2026 to 30th April 2026.

Methods: The SH-SY5Y cells were subjected to corticosterone (100 μM) and H2O2 (100 μM) treatment for 24
hours, after which we used fluoxetine (0.1-50 μM) and photobiomodulation (2.5-60 J/cm2).

Results: Exposure to dual-hits resulted in decreased viability up to 59.6% (p<0.0001). The fluoxetine demonstrated hormesis effect: cell viability reached 102.4% when fluoxetine was used at a concentration of 1 μM. Moreover, there was statistically significant decrease in interleukin-6 (1.42 vs. 3.97 pg/mL), major depressive disorder (8.3 vs. 12.0 mg/dL), and increased levels of glutathione (44.1 vs. 29.2 μM). The photobiomodulation applied at 10 J/cm2 restored viability to 107.1% (p<0.0001) and had similar effect.

Conclusion: Both fluoxetine and 808 nm photobiomodulation confer biphasic neuroprotection in a clinically
relevant dual-hit depression model, establishing dose thresholds for future synergy investigations.