Androstenediol repelled isoflurane-induced behavioral and cognitive insults in neonatal rats: investigating the role of estrogen receptor beta.

Isoflurane (Isof), a commonly used pediatric anesthetic, has been linked to neurotoxicity during brain development, resulting in cognitive impairments and neuroinflammation. Androstenediol (ADIOL), a neurosteroid with anti-inflammatory and anti-oxidant activities, exhibits potential in treating neurodegenerative disorders through estrogen receptor β (ERβ) agonism. Thirty-six newborn male albino rats were randomly allocated to four distinct groups: Control, Isof, ADIOL + Isof, and ADIOL + PHTPP (ERβ antagonist) + Isof. Isof neurotoxicity induced by inhalation of 0.75% Isof for 6 h. ADIOL (25 mg/kg/day) and PHTPP were given subcutaneously for two days before Iso exposure. Behavioral tests (Morris water maze, T-maze, open field, and rotarod test) evaluated spatial learning, memory, exploration, motor functions, and biochemical investigations to evaluate oxidative and inflammatory states. Isof exposure significantly reduced spatial learning and memory, with disturbed exploration behavior of neonatal rats with motor incoordination insults. Isof induced oxidative stress with the inflammatory response. ADIOL administration abates these abnormalities, but co-administration with PHTPP averted ADIOL's protective effects, indicating ERβ-mediated processes. ADIOL reduces Isof-induced neurotoxicity via ERB agonist. Its neuroprotective activity suggests a feasible therapeutic approach to reducing anesthetic-induced developmental neurotoxicity.