Effect of Sertraline and Vortioxetine on Stress-Induced Brain Injury in Rats: Biochemical and Histopathological Evaluations.

Objectives: Our aim was to evaluate the comparative effects of sertraline and vortioxetine against stress-induced brain injury in rats.

Methods: The rats were assigned to a nonstress group (NSG), stress-treated control (StC), sertraline + stress (SSt), and vortioxetine + stress (VSt) groups. Sertraline and vortioxetine (10 mg/kg) were given orally by gavage to the SSt and VSt groups. One hour later, all animals (except NSG) underwent forced immobilization to establish a stress model (2 hours). The drugs were given once a day for 30 days. The animals were killed with ketamine 150 mg/kg, and tissues were removed from the cerebral cortex. One-way analysis of variance and Fisher post hoc least significant difference were conducted for the analysis.

Results: The malondialdehyde (nmol/mL) level was 2.58 ± 0.48 in the NSG, 8.09 ± 0.57 in the StC, 3.84 ± 0.53 in the SSt, and 2.84 ± 0.20 in the VSt group (P < 0.0002). The total glutathione (mmol/g) was 7.15 ± 0.59 in the NSG, 2.41 ± 0.43 in the StC, 4.58 ± 0.26 in the SSt, and 5.98 ± 0.13 in the VSt (P < 0.0002). The total oxidant status (mmol H2O2Eq/L) level was 3.56 ± 0.20 in the NSG, 9.99 ± 0.74 in the StC, 4.97 ± 0.39 in the SSt, and 3.81 ± 0.31 in the VSt (P < 0.0002). The total antioxidant status (mmolTroloxEq/L) level was 8.65 ± 0.37 in the NSG, 3.04 ± 0.22 in the StC, 6.29 ± 0.34 in the SSt, and 7.61 ± 0.40 in the VSt (P < 0.0002). Sertraline reduced pericellular edema in astrocytes and oligodendrocytes and decreased perivascular edema, dilatation, and congestion of blood vessels, whereas these were not seen with vortioxetine.

Conclusions: Compared with sertraline, vortioxetine is a neuroprotective antidepressant with higher antioxidant activity and can more effectively prevent stress-induced brain tissue injury.