Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism.

Abstract

Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the comparative effects of hesperetin (Hst) and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500 mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were VPA-exposed which received hesperetin and nano-hesperetin (10 and 20 mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high level of anxiety-like behaviors (P <  0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido-inflammatory markers. Hesperetin and nano-hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p <  0.05) plasma's inflammation indexes. In conclusion, it can be state that nano-hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation.

• Authors: Rashin Khalaj, Akbar Hajizadeh Moghaddam, Mahboobeh Zare
• Journal: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (Int J Dev Neurosci) Vol. 69 Pg. 80-87 (Oct 2018) ISSN: 1873-474X [Electronic] United States
• PMID: 29966739 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Anticonvulsants
• Antioxidants
• Cytokines
• Valproic Acid
• Hesperidin
• hesperetin

Topics

• Animals
• Anticonvulsants
• Antioxidants (metabolism)
• Autistic Disorder (chemically induced, drug therapy, psychology)
• Birth Weight
• Brain Chemistry (drug effects)
• Cytokines (metabolism)
• Female
• Hesperidin (chemistry, pharmacology, therapeutic use)
• Inflammation (chemically induced, drug therapy, psychology)
• Interpersonal Relations
• Motor Activity (drug effects)
• Nanoparticles
• Oxidative Stress (drug effects)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Rats
• Rats, Wistar
• Social Behavior
• Valproic Acid