Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling

被引:2
|
作者
Alnakhli, Anwar M. [1 ]
Saleh, Asmaa [1 ]
Kabel, Ahmed M. [2 ]
Estfanous, Remon S. [3 ]
Borg, Hany M. [4 ]
Alsufyani, Khulud M. [5 ]
Sabry, Nesreen M. [6 ]
Gomaa, Fatma Alzahraa M. [7 ]
Abd Elmaaboud, Maaly A. [2 ]
机构
[1] Princess Nourah Bint Abdulrahman Univ, Coll Pharm, Dept Pharmaceut Sci, POB 84428, Riyadh 11671, Saudi Arabia
[2] Tanta Univ, Fac Med, Dept Pharmacol, Tanta 31527, Egypt
[3] Tanta Univ, Fac Med, Anat & Embryol Dept, Tanta 31527, Egypt
[4] Kafrelsheikh Univ, Fac Med, Physiol Dept, Kafr El Shaikh 33516, Egypt
[5] Taif Med Ctr, Taif 26526, Saudi Arabia
[6] Tanta Univ, Fac Med, Clin Oncol Dept, Tanta 31527, Egypt
[7] Al Baha Univ, Fac Pharm, Pharamcognosy & Med Herbs Dept, Albaha 65779, Saudi Arabia
来源
MEDICINA-LITHUANIA | 2024年 / 60卷 / 11期
关键词
autism; perindopril; valproic acid; neuroinflammation; apoptosis; rats; OXIDATIVE STRESS; SPECTRUM; INHIBITION;
D O I
10.3390/medicina60111802
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and Objectives: Autism is a developmental disability characterized by impairment of motor functions and social communication together with the development of repetitive or stereotyped behaviors. Neither the exact etiology or the curative treatment of autism are yet completely explored. The goals of this study were to evaluate the possible effects of perindopril on a rat model of autism and to elucidate the possible molecular mechanisms that may contribute to these effects. Materials and Methods: In a rat model of sodium valproate (VPA)-induced autism, the effect of postnatal administration of different doses of perindopril on growth and motor development, social and repetitive behaviors, sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3 beta pathway, JAK2/STAT3 axis, and PPAR-gamma signaling in the hippocampal tissues were investigated. The histopathological and electron microscopic changes elicited by administration of the different treatments were also investigated. Results: Perindopril dose-dependently combatted the effects of prenatal exposure to VPA on growth and maturation, motor development, and social and repetitive behaviors. In addition, the different doses of perindopril ameliorated the effects of prenatal exposure to VPA on sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3 beta pathway, JAK2/STAT3 axis, and PPAR-gamma signaling. These effects had a mitigating impact on VPA-induced histopathological and electron microscopic changes in the hippocampal tissues. Conclusions: Perindopril may emerge as a promising agent for amelioration of the pathologic changes of autism spectrum disorders.
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页数:24
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