Gallic acid partially attenuates thiomersal-associated oxidative, apoptotic, and CREB/BDNF-related alterations in rat hippocampal and prefrontal cortex tissues and systemic inflammatory responses.

Thiomersal (THIM), an organomercury preservative, has been associated with oxidative stress-related neurotoxicity. This study investigated the effects of gallic acid (GA) on THIM-associated oxidative, apoptotic, and CREB/BDNF-related molecular alterations in brain tissue and systemic inflammatory responses in rats. Twenty-eight male Wistar albino rats were assigned to Control, THIM, GA, and THIM+GA groups (n = 7/group). THIM (25 µg/kg, intraperitoneally) was administered at 10-day intervals, whereas GA (50 mg/kg/day, oral gavage) was given for 20 consecutive days. MDA, SOD, CAT, and GSH were measured in combined hippocampal and prefrontal cortex homogenates; serum MDA, IL-1β, IL-6, and TNF-α were also assessed. Bax, Bcl-2, Casp-3, CREB, and BDNF mRNA expression was analyzed by RT-qPCR. THIM increased tissue MDA (0.44 ± 0.06 vs. 1.06 ± 0.15 nmol/mg protein, p < 0.0001) and serum TNF-α (93.9 ± 9.6 vs. 171.3 ± 8.8 ng/L, p < 0.0001) and reduced BDNF mRNA expression (1.01 ± 0.15 vs. 0.41 ± 0.17, p = 0.0001). In THIM-exposed animals, GA reduced tissue MDA and serum TNF-α and increased BDNF expression (all p < 0.05). Significant THIM × GA interactions were identified for tissue CAT, GSH, MDA, Bax/Bcl-2 ratio, BDNF, and serum MDA, IL-1β, IL-6, and TNF-α. Simple-effects analyses indicated that GA effects were mainly evident during THIM exposure. These findings suggest that GA partially attenuates THIM-associated oxidative and apoptosis-related molecular alterations, systemic inflammatory responses, and BDNF-related transcriptional changes.