Cisplatin is one of the most widely used chemotherapy drugs, but its clinical value is limited by serious side effects, including damage to the nervous system. A new rat study published in Molecular Biology Reports examined whether tert-butylhydroquinone, an antioxidant compound better known as TBHQ, could protect the brain from cisplatin-induced neurotoxicity. The researchers report that co-administration of TBHQ eased several of the cognitive, biochemical and histological changes produced by the chemotherapy agent.

In the study, rats were randomly assigned to five groups of six animals each: a control group, a cisplatin group, a vehicle group, a TBHQ-only group, and a group receiving both cisplatin and TBHQ. The researchers then assessed cognition and behavior using the Morris Water Maze, a standard test of spatial learning and memory, together with the Open Field Test, which measures general activity and anxiety-related behavior.

The behavioral results pointed to a learning deficit caused by cisplatin. On day 2 of training in the Morris Water Maze, rats treated with cisplatin took significantly longer to reach a hidden platform than controls, with an escape latency of 38.63 plus or minus 15.77 seconds compared with 14.25 plus or minus 5.82 seconds in the control group, a difference that reached statistical significance at p = 0.014. This early-training impairment suggests that cisplatin interfered with the rapid acquisition of spatial information rather than performance on a single trial.

TBHQ co-administration appeared to counter much of this deficit. Rats receiving both cisplatin and TBHQ showed a day 2 escape latency of 19.04 plus or minus 7.77 seconds, significantly shorter than the cisplatin group’s 38.63 seconds at p = 0.044. The protective effect was most evident during the early learning phase, indicating that the compound helped preserve the cognitive functions most sensitive to the chemotherapy drug.

Blood chemistry told a parallel story. Cisplatin treatment was associated with significantly lower serum levels of the antioxidant enzymes and molecules superoxide dismutase, catalase and glutathione, alongside elevated serum malondialdehyde, a marker of lipid peroxidation and oxidative damage, all at p < 0.05. Together, these biochemical changes indicate a shift in serum antioxidant and oxidant markers in cisplatin-treated rats.

Direct examination of hippocampal tissue added further evidence of injury. Histopathological analysis revealed hemorrhagic foci in the hippocampal tissues of cisplatin-treated rats. Immunohistochemical staining then quantified molecular changes: cisplatin increased immunoreactivity for the inflammatory markers TNF-alpha and IL-6 and decreased immunoreactivity for neurogranin, a protein involved in synaptic plasticity, with all three changes significant at p < 0.0001.

The authors conclude that cisplatin administration produced potent neurotoxicity in this model, severely impairing spatial learning while altering both neurogranin and inflammatory markers, and that TBHQ administration was associated with attenuation of the cognitive deficits and biochemical alterations. They caution appropriately that TBHQ, given its defined profile, may warrant further investigation for mitigating chemotherapy-induced neurotoxicity rather than presenting it as an established therapy.

Subject of Research: Neuroprotective effects of tert-butylhydroquinone against cisplatin-induced neurotoxicity in rats

Article Title: Effects of tert-butylhydroquinone on cisplatin-induced neurotoxicity in rats

Article References: Yigit, S., Bitiktas, S., Yeşilyurt, İ., Gul, H. F., Gulakar, B., Aydın, Z. C., & Kahraman, A. A. (2026). Effects of tert-butylhydroquinone on cisplatin-induced neurotoxicity in rats. Molecular Biology Reports, 53(1), Article 1794. https://doi.org/10.1007/s11033-026-12986-2

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12986-2

Keywords: cisplatin, neurotoxicity, TBHQ, tert-butylhydroquinone, oxidative stress, Morris Water Maze, hippocampus, neurogranin, TNF-alpha, IL-6, rats, chemotherapy