Abstract
Diethylnitrosamine (DEN), a common dietary carcinogen, is associated with neurotoxicity in humans and animals. This study investigated the neuroprotective effects of diphenyl diselenide (DPDS) against DEN-induced neurotoxicity in male Albino Wistar rats (n = 40). Rats were randomly distributed into cohorts and treated as follows: vehicle control (corn oil 2 mL/kg; gavage), DPDS-only (5 mg/kg; gavage) and DEN-only (200 mg/kg; single dose i.p.). Also, two other rat cohorts were pre-treated with DPDS (3 or 5 mg/kg) for 15 days (day: 0-15), subsequently administered with DEN (200 mg/kg) and continuously treated with DPDS for another 7 days, (days:15-21). Behavioural tests (OFT- using the open field test; NORT- novel object recognition test; FST- forced swimming test and Y-maze) were conducted from days 19-21, followed by biochemical analysis of the hippocampus and prefrontal cortex for oxidative stress, inflammation, neurotransmitter metabolic enzyme, and histopathology. DEN-treated rats exhibited decreased locomotor activity, spatial memory function and antioxidant activity, increased oxidative and nitration stress, anxiety, and depressive-like behaviour, causing histoarchitectural damage in prefrontal and hippocampal cortices. DPDS treatment (pre- and post-DEN exposure) significantly alleviated these neurotoxic, oxidative, and nitration effects, reversed DEN-induced histopathological alterations, and improved locomotive and cognitive functions. In conclusion, DPDS demonstrates potent neuroprotective effects against DEN-induced toxicity, likely through enhanced endogenous antioxidant capacity that mitigates oxido-nitrative damage. These findings suggest that the organo-selenium -DPDS- is a promising chemotherapeutic agent potent in alleviating DEN-mediated neurotoxicity and maintaining brain health.