Abstract Background Chronic inhalation of cellulosic thinner, which contains toluene and other volatile solvents, induces oxidative stress–mediated neurotoxicity, particularly within the nucleus accumbens (NAc). This study evaluated the neuroprotective effects of melatonin and cortistatin against thinner-induced NAc injury. Methods Ninety male Wistar rats were assigned to nine groups (n = 10): control, thinner-only, thinner + cortistatin, thinner + melatonin, thinner + melatonin + cortistatin, and four vehicle controls. Rats were exposed to thinner vapour twice daily (1 h/session) for six weeks. Melatonin (10 mg/kg) and/or cortistatin were administered intraperitoneally once daily. NAc tissue was analysed by light microscopy, transmission electron microscopy, and biochemical assays of lipid peroxidation (MDA) and antioxidant enzymes (GPx, SOD, CAT). Results Thinner inhalation induced behavioral changes, fur discoloration, and significant weight loss ( p 0.05). Glutathione peroxidase was reduced in the thinner group vs. control (0.36 vs. 0.56, p = 0.046). Superoxide dismutase activity was lower in thinner (1.93 vs. 3.67, p < 0.001) and thinner + cortistatin (2.82 vs. 3.67, p = 0.028) groups, with melatonin mitigating reductions. Lipid peroxidation was elevated in the thinner group (3.59 vs. 2.38, p = 0.042), though overall group differences were not significant ( p = 0.127). Conclusions Chronic thinner inhalation causes oxidative stress–related degeneration of the NAc. Melatonin and cortistatin exert neuroprotective effects, with their combination offering superior preservation of cellular and biochemical integrity. These findings highlight potential therapeutic avenues for solvent-induced neurotoxicity.
Önder et al. (2026) studied this question.