LAUSR

&NA; Estradiol (E2), in addition to its known hormone function, is a neuroactive steroid that has shown neuroprotective profile in several models of neurological diseases. The present study explores the antioxidant effect of &bgr;‐estradiol‐3‐benzoate (EB) on the neurotoxicity elicited by MPP+ in rat striatum. Male Wistar rats, that were gonadectomized 30 days prior to EB, were given 100 &mgr;g EB per rat every 48 h for 11 days and animals were infused with MPP+ via intrastriatal at day six after beginning EB treatment. EB treatment completely prevented the fall in dopamine caused by MPP+, such result was related with decreased lipid peroxidation, a marker of oxidative stress; diminished number of ipsilateral‐to‐lesion turns and increased signal of the dopamine‐synthesizing enzyme Tyrosin Hydroxylase in substantia nigra. The protection elicited by EB was not related to Mn or Cu‐Zn superoxide dismutase enzymatic activities or glutathione modulation since none of these parameters were influenced by EB at the times assayed. Whereas, increased expression of PON2 as a result of EB treatment was observed, this phenomenon could be one of the mechanism by which the steroid conferred protection to dopaminergic cells against MPP+ injury. HighlightsSystemic estradiol spared dopaminergic cell from death induced by MPP+.Estradiol treatment prevented dopamine loss induced by MPP+ in rat striatum.Estradiol reduced lipid oxidation induced by MPP+, fact unrelated to SOD or GSH.Estradiol increased PON2 expression in brain, possibly related to decreased lipid oxidation.