Khalaj Rashin, Hajizadeh Moghaddam Akbar, Zare Mahboobeh
Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
Department of Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
Int J Dev Neurosci. 2018 Oct;69:80-87. doi: 10.1016/j.ijdevneu.2018.06.009. Epub 2018 Jun 30.
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.
产前暴露于丙戊酸（VPA）会诱发自闭症谱系障碍（ASD）中的行为障碍并增强氧化炎症应激。本研究的目的是调查橙皮素（Hst）和纳米橙皮素对产前暴露于丙戊酸的大鼠后代的社会行为缺陷和氧化炎症指标的比较影响。在胚胎第0天（E0）的怀孕Wistar大鼠被分为六组；第1组作为对照组，从E1开始直至哺乳期结束口服蒸馏水（PO），并在E12.5腹腔注射（i.p）生理盐水。第2组在E12.5接受丙戊酸钠（500mg/kg溶于0.9%生理盐水中，i.p），被视为VPA暴露组，第3至6组为VPA暴露组，分别从E0开始直至哺乳期结束接受橙皮素和纳米橙皮素（10和20mg/kg/天，PO）。在出生后第28天（PND 28）和PND 30进行社会互动和旷场试验，在PND 28和PND 30评估脑抗氧化酶活性和生化指标、血浆中炎症因子水平以及小脑组织病理学。产前暴露于丙戊酸的大鼠表现出社交能力差和高水平的焦虑样行为（P<0.05）。此外，通过测定不同的氧化炎症标志物发现氧化应激和炎症水平升高。橙皮素和纳米橙皮素治疗改善了行为障碍并降低了脑中的氧化应激以及显著降低了（p<0.05）血浆炎症指标。总之，可以说与橙皮素相比，纳米橙皮素具有神经保护作用，并且在怀孕和哺乳期对VPA自闭症动物模型的治疗可能有效。
