Neuroprotective Effects of Bryophyllum pinnatum against Ketamine-Induced Neurotoxicity in Wistar Rats: Neurochemical, Oxidative Stress, and Histological Investigation

Background: This study evaluated the neuroprotective effects of Bryophyllum pinnatum (B. pinnatum) in ketamine-induced neurotoxicity in Wistar rats, focusing on neurochemical and oxidative stress markers, as well as histological changes in the hippocampus and cerebral cortex. Methods: Sixty male Wistar rats were divided into six groups. Group 1 received normal saline (2ml), Group 2 was administered ketamine (20mg/kg), and Group 3 received risperidone (0.5mg/kg). Groups 4, 5, and 6 were treated with B. pinnatum at 50mg/kg, 100mg/kg, and 200mg/kg, respectively for a duration of 21 days after induction of toxicity. Neurochemical markers (dopamine, glutamate, GABA, serotonin, noradrenaline, acetylcholine), oxidative stress markers (GSH, MDA, SOD, CAT, GPx), and histological analysis of brain tissues were evaluated after treatment periods of one, two, and three weeks. Results: Ketamine administration significantly reduced dopamine, GABA, serotonin, and noradrenaline levels while increasing acetylcholine and glutamate levels (p<0.05). B. pinnatum treatment reversed these effects in a dose-dependent manner, particularly at high doses. Oxidative markers showed reduced GSH and increased MDA levels with ketamine, which B. pinnatum mitigated significantly (p<0.05). Histologically, ketamine caused neuronal degeneration and microstructural distortion in the hippocampus and cerebral cortex, which were markedly reduced by B. pinnatum, especially at 200mg/kg, showing well-preserved neuronal structures. Conclusion: B. pinnatum demonstrates significant neuroprotective effects against ketamine-induced neurotoxicity by modulating neurochemical and oxidative markers and preserving histological integrity in brain tissues, suggesting its potential therapeutic application in neurotoxic conditions.