Camphene Mitigates Cyclophosphamide-Induced Oxidative Stress, Neuroinflammation, and Cognitive Dysfunction via Nrf2, NF-κB, and Astrocytic GFAP Modulation in Wistar Albino Rats

Abstract

Cyclophosphamide (CP) is a potent chemotherapeutic medication for various cancer types. Chemotherapy-associated neurotoxicity is a significant adverse effect seen in cancer patients undergoing treatment with cyclophosphamide. The root cause of this toxicity is the production of reactive oxygen species (ROS). Camphene (CAMP) is a natural substance that has demonstrated its effectiveness as a potent antioxidant and anti-inflammatory molecule. Hence, we have selected Camphene to evaluate its potential role in mitigating CP-induced neurotoxicity in rats. CAMP was administered orally at 50, 100, and 200 mg/kg doses from Day 1 to Day 21. On Day 7, the rats were administered with CP at 200 mg/kg via intraperitoneal injection. Neurobehavioral assessments including elevated plus maze test (EPM), forced swim test (FST), grip strength test (GST), and sucrose preference test (SPT) were performed. On Day 21, the rats were euthanized, and their brains were extracted for examining histopathological, Immunohistochemical, Oxidative stress and Anti-inflammatory parameters. Nuclear Factor kappa B (NF-κB), Nuclear Factor Erythroid 2–related Factor 2 (Nrf2), Glial Fibrillary Acidic Protein (GFAP), Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR), Thiobarbituric Acid Reactive Substances (TBARS), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), and Tumour Necrosis Factor-alpha (TNF-α) were assessed. Camphene at 100 and 200 mg/kg exhibited neuroprotective effects and prevented neurological disorders induced by cyclophosphamide (CP) at 200 mg/kg by reversing oxidative stress, inflammation, and neurobehavioral changes. Camphene, thus, exhibited dose-dependent neuroprotection by increasing antioxidant level, decreasing neuroinflammation, and enhancing behavioural outcomes.