Farbin Mitra, Hejazi Anahita, Fakhraei Nahid, Azizi Yaser, Mehrabi Soraya, Hajisoltani Razieh
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Physiology Department, Iran University of Medical Sciences, Tehran, Iran.
IBRO Neurosci Rep. 2024 Oct 30;17:493-502. doi: 10.1016/j.ibneur.2024.10.003. eCollection 2024 Dec.
Valproic acid (VPA) demonstrates teratogenic effects during pregnancy. Prenatal exposure to VPA may result in autism spectrum disorder (ASD) -like phenotypes. Apigenin, a natural flavonoid, has been shown to have neuroprotective impacts due to its antioxidant properties. This study aimed to investigate the protective effects of apigenin in prenatal Valproic acid-induced autism in rats. Female rats (220-240 g, 2-3 months) received a single dose of VPA (600 mg/kg, i.p.) on the 12.5th day of gestational. The male offspring were given oral apigenin (50 mg/kg, p.o.) or the vehicle for 30 days. Behavioral tests, biochemical assessments for oxidative stress markers and pro-inflammatory cytokines were performed. VPA-treated rats exhibited increased anxiety-like behavior, and repetitive behavior. Social interaction was reduced, and detection of the novel object was impaired. Also, VPA-treated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GPX and superoxide dismutase (SOD) levels. Furthermore, IL-6 and TNF-α increased in the prefrotalcortex decreased. On the other hand, apigenin-treated rats restored the cognitive consequences and lowered oxidative stress and inflammation in the prefrotalcortex.
Chronic apigenin treatment restored the behavioral and biochemical abnormalities caused by prenatal VPA exposure.
丙戊酸(VPA)在孕期具有致畸作用。产前暴露于VPA可能导致自闭症谱系障碍(ASD)样表型。芹菜素是一种天然黄酮类化合物,因其抗氧化特性已被证明具有神经保护作用。本研究旨在探讨芹菜素对产前丙戊酸诱导的大鼠自闭症的保护作用。雌性大鼠(220 - 240克,2 - 3个月)在妊娠第12.5天接受单次剂量的VPA(600毫克/千克,腹腔注射)。雄性后代口服芹菜素(50毫克/千克,口服)或赋形剂30天。进行行为测试、氧化应激标志物和促炎细胞因子的生化评估。VPA处理的大鼠表现出焦虑样行为增加和重复行为。社交互动减少,对新物体的探测受损。此外,VPA处理的大鼠氧化应激丙二醛(MDA)水平较高,谷胱甘肽过氧化物酶(GPX)和超氧化物歧化酶(SOD)水平较低。此外,前额叶皮质中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)增加。另一方面,芹菜素处理的大鼠恢复了认知结果,并降低了前额叶皮质中的氧化应激和炎症。
长期芹菜素治疗恢复了产前VPA暴露引起的行为和生化异常。