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

Introduction: uteroplacental insufficiency (upi) produces critical neurodevelopmentalproblems affecting the intrauterine growth restricted (iugr) in offspring. this study aimedto investigate the possible neuroprotective roles of hesperidin (hes) on the fetal cerebral cortexof the upi rat model.methods: in this experimental study, 40 pregnant wistar rats (age: ~40 days, mean±sdweight: 180±10 g) were randomly divided into 5 groups (n= 8/group). the study groupsincluded 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 100mg/kg hes, orally). after being anesthetized by ketamine and xylazine, upi was induced bypermanent bilateral closure of the uterine vessels on gestation day (gd) 18. from gd15, thehes/ns-treated groups received hes/normal saline until gd21. on gd21, the uterus, placenta,and fetus were dissected out and weighed. the oxidative stress parameters, including catalase(cat) activity, malondialdehyde (mda), and total antioxidant capacity (tac) weremeasured in the fetal cerebral cortex. the expression of brain-derived neurotrophic factor(bdnf) and tropomyosin receptor kinase b (trkb) was assessed by rt qpcr methods.the obtained data were analyzed by analysis of variance (anova) and tukey’s post hoc test.results: the present study findings identified a significant difference in the uterine and fetusweight in hes-treated mothers (p< 0.05). in the fetus, hes reduced mda, and increased catactivity and tac (p˂0.001 in the upi+hes100 group, compared to the upi+ns group). upireduced 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 administratinghes in the fetal cerebral cortex of the upi rat model, in a dose-dependent manner (p<0.05).conclusion: hes, as a neuroprotective and antioxidant agent, accelerates bdnf-trkb signalingpathway and suppresses oxidative stress parameters in the cerebral cortex of the upi rat model.