Evaluation of aromatase inhibitors against seizures and neurotoxicity in mice

Abstract

Neurosteroids such as testosterone and its metabolites play a major role in the neuroendocrine control of brain excitability and seizure susceptibility. Testosterone gets metabolized by aromatase and 5and#945;-reductase enzyme to distinct neurosteroids which show both proconvulsant and anticonvulsant effects respectively.The present study evaluated whether inhibition of aromatase, by aromatase inhibitor protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Also to formulate nanoformulation of aromatase inhibitor for selective targeting in brain. Nanoformulation was assessed for antiepileptic and neuroprotective effects. newlineOur findings demonstrate the anticonvulsant potential of LET. The above observed effects could be probably due to inhibition of aromatase and diverting the pathway to 3and#945;-Diol with known anticonvulsant and neuroprotective action. The LET-NE was developed for the direct nose to brain delivery which appears to be a promising approach for minimizing the peripheral side effects of letrozole. The pharmacodynamics study demonstrated the improved anticonvulsant and additional neuroprotective effect of LET-NE as compared to LET against KA-induced seizures in mice, as intranasal administration of LET-NE improved the brain uptake of letrozole as compared with the i.p. route due to direct nose-to-brain delivery. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of epileptic seizures and can be pursued further. newline