Neuroprotective role of n-acetylcysteine (NAC): countering doxorubicin neurotoxicity via TH, Nurr1, and iNOS expression

Chemotherapy is an effective treatment for cancer, but it can cause cognitive disorders broadly referred to as “chemobrain.” One of the most commonly used chemotherapeutics, doxorubicin (DOX), has been associated with the potential for brain damage and cognitive dysfunction. N-acetylcysteine (NAC) has been identified as a potential brain protector with antiapoptotic, antioxidant, and anti-inflammatory effects. The objective of this study was to investigate the potential protective effect of NAC against DOX-induced brain damage. Female Wistar albino rats were randomly assigned to one of three groups: control, DOX, or NAC prophylaxis. Brain samples were collected for histopathological and immunohistochemical analyses, with a particular focus on regions that are crucial for cognition and memory. The DOX group exhibited significant histopathological changes, including neuronal shrinkage, degeneration, and necrosis in the striatum, hippocampal region, and cerebral cortex. Immunohistochemical analysis revealed the presence of neuroinflammation and neurodegeneration, with an increase in inducible nitric oxide synthetase (iNOS) immunopositivity. Administration of NAC effectively reduced iNOS immunopositivity, neuronal damage, degeneration, and necrosis in the prophylaxis group. Among the brain regions examined, the prophylaxis group demonstrated the most effective protection in the hippocampal region. Therefore, NAC has the potential to protect against or alleviate DOX-induced cognitive impairments.