Effects of tert-butylhydroquinone on cisplatin-induced neurotoxicity in rats

Cisplatin (Cis) is a potent chemotherapy agent with limited clinical use due to serious side effects, including neurotoxicity. This study investigated the neuroprotective effects of tert-butylhydroquinone (TBHQ) against Cis-induced neurotoxicity.

Rats were randomly divided into five groups (n = 6 per group): Control, Cis, Vehicle, TBHQ, and Cis+TBHQ. Cognitive and behavioral changes were assessed using the Morris Water Maze (MWM) and the Open Field Test. Serum samples were analyzed for antioxidant/oxidant markers (SOD, CAT, GSH, and MDA), and hippocampal tissues were evaluated histopathologically and immunohistochemically (TNF-α, IL-6, and neurogranin).

In the MWM test, escape latency to the hidden platform on day 2 of training was significantly longer in the Cis group than in the control group (38.63 ± 15.77 s vs. 14.25 ± 5.82 s, p = 0.014). In contrast, TBHQ co-administration (Cis+TBHQ) alleviated these cognitive deficits, particularly during early learning, significantly reducing day 2 escape latency to 19.04 ± 7.77 s compared with the Cis group (38.63 ± 15.77 s, p = 0.044). Biochemically, Cis was associated with decreased serum SOD, CAT, and GSH and increased serum MDA (p < 0.05). Histopathologically, hemorrhagic foci were observed in the Cis group. Furthermore, immunohistochemical analysis revealed that Cis was associated with increased TNF-α and IL-6 immunoreactivity (p < 0.0001) and decreased neurogranin immunoreactivity (p < 0.0001).

Collectively, Cis administration causes potent neurotoxicity, severely impairs spatial learning, and alters plasticity-associated marker neurogranin and inflammatory markers. Specifically, TBHQ administration was associated with the attenuation of Cis-induced cognitive deficits and biochemical alterations. Given its defined profile, TBHQ may warrant further investigation for mitigating chemotherapy-induced neurotoxicity.