Oxidative stress level and histopathological changes in the rat brain following separate and combined administration of cisplatin and dexamethasone.

Neurotoxicity is one of the most serious complications associated with cisplatin chemotherapy, limiting its clinical use at higher doses that may be more effective. To mitigate adverse effects caused by cisplatin-induced oxidative stress, dexamethasone is often included in chemotherapy protocols due to its anti-inflammatory and immunomodulatory properties. This study aimed to identify a correlation between oxidative stress and histological changes in rat brain tissue following the single dose of intraperitoneal injection of cisplatin (8 mg/kg) and dexamethasone (4 mg/kg)in the case of separate and combined use. Biochemical analyses revealed that cisplatin and dexamethasone increased levels of malondialdehyde and decreased the activities of catalase and superoxide dismutase to varying extents after separate and combined exposure to these drugs. Histomorphological examinations showed neuronal degeneration, cytoplasmic shrinkage, and severe cytoarchitectural alterations in both hippocampal and cortical areas after separate treatments with each drug. These findings suggest that both agents exhibit pro-oxidant and neurotoxic effects. Interestingly, the combined administration of cisplatin and dexamethasone did not lead to a synergistic increase in lipid peroxidation or structural damage; instead, dexamethasone partially attenuated cisplatin-induced neurotoxicity. These findings suggest that cisplatin and dexamethasone exert their effects through different molecular mechanisms, which probably determine both the different strength of these pro-oxidant effects and the different histological changes, both individually and as a result of their combined use.