Oral mucositis is a common yet often overlooked complication of chemotherapy. Although paclitaxel (PTX) is a potent anticancer agent, it induces various pathologies in the oral tissues. Pumpkin seed oil (PSO) was prized significant pharmacological properties that can produce health-protective effects. The study aimed to highlight the effects of PTX on the dorsal tongue mucosa of rats and assess the alleviative role of PSO focusing on the underlying mechanisms. Forty rats were divided into: Control, PSO, PTX, and PTX + PSO. PTX was administered intraperitoneally at a dose of 2 mg/kg once weekly, while PSO was given orally at 1.5 ml/kg daily, both for 6 consecutive weeks. Tongue tissues were subjected to histological, immunohistochemical, biochemical and RT-qPCR analyses. PTX group exhibited a loss of the normal papillary architecture of the dorsal tongue mucosa. There was a statistically significant reduction in the epithelial thickness, the height and width of the papillae and proliferating cell nuclear antigen (PCNA) immunoreactivity. Malondialdehyde (MDA) levels were significantly elevated, while glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels were markedly decreased. A significant upregulation of NF-κβ, TNF-α, IL-1β, IL-18, and IL-6 mRNA expression was observed denoting markedly fired inflammatory cascade. PSO + PTX group showed significant mitigation of these molecular alterations which were translated into structural conservation with no significant difference when compared to the control group. PTX triggers inflammation and oxidative stress, leading to epithelial proliferation arrest. PSO, antioxidant and anti-inflammatory rescuer, effectively preserves the structural integrity of the dorsal tongue mucosa.
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