Amelioration of diethylnitrosamine-induced acute brain injury by α-eudesmol and β-eudesmol.

Diethylnitrosamine (DEN) is a widely distributed environmental pollutant known for its toxicity and carcinogenicity in various animal species. The aim of the study was to investigate the neuroprotective effects of α-eudesmol and β-eudesmol against DEN-induced brain damage in rats. Sprague-Dawley rats received a single intraperitoneal dose of DEN (200 mg/kg), followed by intravenous administration of α-eudesmol or β-eudesmol (1 mg/kg) three times weekly for 21 days. Brain tissues were collected for histological, biochemical, and immunohistochemical analyses, including markers of brain injury (c-fos) and apoptosis (caspase 3). DEN exposure significantly decreased antioxidant enzyme activities (catalase, glutathione peroxidase, and superoxide dismutase) and increased oxidative stress marker malondialdehyde. It also triggered platelet activation, inflammatory cytokine production, and pathological changes in brain tissue, accompanied by upregulated c-fos and caspase 3 expression. Treatment with α-eudesmol and β-eudesmol effectively mitigated these alterations by modulating the NF-κB/COX-2/TNF-α/IL-6 signaling pathways and restoring dopamine levels to near control values. These findings highlight the potential of α-eudesmol and β-eudesmol as therapeutic agents against DEN-induced neurotoxicity.