The Ameliorative Effect of Apigenin or Silymarin as Add-On Therapy to Risperidone on Valproic Acid Induced Autism in Albino Rats: Implication of Oxidative Stress, Apoptosis and Autophagy

Abstract

Background: Recent studies show that deficient autophagy, increased mammalian target of rapamycin (mTOR), oxidative stress and apoptosis have a critical role in the pathophysiology of autism. The objective of the current study is to evaluate and compare some possible ameliorative effects of apigenin, silymarin either alone or in combination with risperidone on autism induced by valproic acid (VPA) in albino rats concerning; oxidative stress, autophagy, apoptosis as well as histopathological examination & behavioral tests. Methodology: This experiment was performed on 70 male Wister albino rats divided into seven equal groups; control group; 10 rat pups from control female rats and the other 60 rat pups from female rats that received i.p VPA during pregnancy for other groups as follows untreated VPA-induced autism, risperidone treated group, apigenin treated group, silymarin treated group, apigenin and risperidone treated group, silymarin and risperidone treated group. All treatments were given from post-natal day (PND) 21 st to 40 th. behavioral tests were performed at the end of treatment. Portions of hippocampus were dissected and processed for assessment of biochemical parameters, histopathological examination and immunohistochemistry. Results and conclusion: The findings suggest that apigenin and silymarin produce promising effects in VPA-induced autism as they decrease oxidative stress and apoptosis; in addition, they produce modulation of autophagy with inhibition of mTOR, that all are reflected as amelioration of impaired behavior & improvement of the histopathological picture. Moreover, the use of apigenin or silymarin in combination with risperidone exhibits better and more satisfactory results than in either remedy alone.