Diphenyl diselenide modulates antioxidant status, inflammatory and redox-sensitive genes in diesel exhaust particle-induced neurotoxicity

Abstract

This study seeks to determine the influence of diphenyl diselenide (DPDSe) on redox status, inflammatory and redox-sensitive genes in diesel exhaust particle (DEP)-induced neurotoxicity in male albino rats. Male Wistar albino rats were administered nasally with DEP (30 and 60 μg/kg) and treated with intraperitoneal administration of 10 mg/kg DPDSe. Non-enzymatic (lipid peroxidation and conjugated diene concentrations) and enzymatic (catalase, superoxide dismutase, glutathione peroxidase) antioxidant indices and activity of acetylcholinesterase enzyme were evaluated in brain tissues of the rats. Furthermore, the expression of genes linked to oxidative stress (HO-1, Nrf2), pro-inflammatory (NF-KB, IL-8, TNF-α) anti-inflammatory (IL-10) and brain-specific (GFAP, ENO-2) genes were also determined. The results indicated that DPDSe caused a notable reduction in the high levels of thiobarbituric acid reactive substances and conjugated diene observed in the brain of DEP-administered rats. DPDSe also reversed the observed reduction in catalase, superoxide dismutase and glutathione peroxidase enzyme activities in the brain of DEP-administered rats. Lastly, the downregulation of genes associated with redox homeostasis, anti-inflammatory and brain-specific genes and upregulation of pro-inflammatory genes observed in the DEP-treated groups were ameliorated by DPDSe. The immediate restoration of altered biochemical conditions and molecular expression in the brain of DEP-treated rats by DPDSe further validates its use as a promising therapeutic candidate for restoring neurotoxicity linked with DEP-induced oxidative stress.