The Effects of Hesperidin on BDNF/TrkB Signaling Pathway and Oxidative Stress Parameters in the Cerebral Cortex of the Utero-placental Insufficiency Fetal Rat Model

Abstract

Introduction: Uteroplacental insufficiency (UPI) produces critical neurodevelopmental problems affecting the intrauterine growth restricted (IUGR) in offspring. In this study, it was aimed to investigate the possible neuroprotective roles of hesperidin (Hes) on the fetal cerebral cortex of the UPI rat model. Methods: In this experimental study, 40 pregnant Wistar rats (age:~40-day old, weight: 180±10g) were randomly divided into 5 groups (n=8), includeing control (normal saline, orally), UPI+NS (uterine vessel ligation+normal saline, orally), UPI+HES25, UPI+HES50 and UPI+HES100 (uterine vessel ligation+25, 50 and 100 mg/kg hesperidin, orally). After being anesthetized by ketamine and xylazine, UPI was induced by permanent bilateral closure of the uterine vessels on gestation day (GD) 18. From GD15, the Hes/NS- treated groups received Hesperidin/normal saline until GD21. On GD21, uterus, placenta and fetus were dissected out and weighed. The oxidative stress parameters, including catalase (CAT) activity, malondialdehyde (MDA), and total antioxidant capacity (TAC) in the fetal cerebral cortex were measured. The expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) was assessed by RT qPCR methods. Data were analyzed by ANOVA and Tukey’s post hoc test. Results: Findings showed a significant difference in the uterine and fetus weight in Hes-treated mothers (p< 0.05). In fetus, Hes reduced MDA, and increased CAT activity and TAC (p ˂ 0.001 in the UPI+Hes100 group compared to the UPI+NS group). UPI reduced BDNF and TrkB mRNA expression compared to the control group (p< 0.05). Also, Significant increases in BDNF and TrkB mRNA expression were observed after administration of Hes in the fetal cerebral cortex of the UPI rat model, in a dose dependent manner (p< 0.05). Conclusion: Hesperidin; as a neuroprotective and antioxidant agent; accelerates BDNF-TrkB signaling pathway and suppresses oxidative stress parameters in the cerebral cortex of the UPI rat model.

Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid

“…Then 100 μL of reagent R3 and 10 μL of reagent R4 were added and remixed. The absorbance was read using an ELISA reader at a wavelength of 405 nm, and then the amount of CAT was calculated (Abdollahi et al., 2021 ).…”