Neuroprotective potential of chrysin against ketamine-induced neurotoxicity: Effects on behavioral changes, oxidative stress, and neuroinflammation.

Aim

Ketamine (KTM) is widely used in clinical settings for its anesthetic, analgesic, and antidepressant properties. However, prolonged or repeated KTM exposure can induce neurotoxicity through oxidative stress, neuroinflammation, and apoptotic mechanisms. This study investigated the neuroprotective effects of Chrysin (CHR), a natural flavonoid with potent antioxidant and anti-inflammatory properties, against KTM-induced neurotoxicity in rats.

Methods

Adult male Wistar rats were divided into five groups (n = 7): Control, KTM, CHR KTM + CHR25 and KTM + CHR50. Following a 10-day treatment regimen (KTM:30 mg/kg, i.p.; CHR: 25 or 50 mg/kg, p.o.) cognitive function was assessed using the Morris Water Maze test.

Results

Biochemical analyses revealed that KTM significantly increased MDA levels while decreasing GSH levels and antioxidant enzyme (SOD,CAT,GPx) activities in brain and hippocampus tissues. KTM also upregulated pro-inflammatory (NF-κB,TNF-α,iNOS) and pro-apoptotic (Bax,Caspase-3) markers while downregulating anti-apoptotic Bcl-2 and CaMKII isoforms. Histopathological examination showed that KTM induced neuronal degeneration, necrosis, and vascular hyperemia in cerebral cortex and hippocampus, while immunohistochemical analysis revealed increased GFAP and Caspase-3 immunopositivity. CHR treatment, particularly at the higher dose, significantly ameliorated these histopathological alterations and reduced GFAP and Caspase-3 expression.

Conclusion

These findings suggest that CHR represents a promising adjunctive neuroprotective agent that could mitigate KTM-associated neurotoxicity while preserving its therapeutic applications.