Hesperidin pretreatment protects hypoxia-ischemic brain injury in neonatal rat.
Neonatal hypoxia-ischemic encephalopathy (HIE) remains a major cause of brain damage, leading to high disability and mortality rates in neonates. In vitro studies have shown that hesperidin, a flavanone glycoside found abundantly in citrus fruits, acts as an antioxidant. Although hesperidin has been considered as a potential treatment for HIE, its effects have not been fully evaluated. In this study, the protective effect of hesperidin pretreatment against hypoxia-ischemic (HI) brain injury and possible signal pathways were investigated using in vivo and in vitro models. In vivo HI model employed unilateral carotid ligation in postnatal day 7 rat with exposure to 8% hypoxia for 2.5h, whereas in vitro model employed primary cortical neurons of neonatal rats subjected to oxygen and glucose deprivation for 2.5h. Hesperidin pretreatment significantly reduced HI-induced brain tissue loss and improved neurological outcomes as shown in 2,3,5-triphenyltetrazolium chloride monohydrate staining and foot-fault results. The neuroprotective effects of hesperidin are likely the results of preventing an increase in intracellular reactive oxygen species and lipid peroxide levels. Hesperidin treatment also activated a key survival signaling kinase, Akt, and suppressed the P-FoxO3 level. Hesperidin pretreatment protected neonatal HIE by reducing free radicals and activating phosphorylated Akt.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Z
Z
Rong
R
R
Pan
Y
Y
Xu
C
C
Zhang
Y
Y
Cao
D
D
Liu
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D006569:Hesperidin / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D006569:Hesperidin
2,3,5-triphenyltetrazolium chloride monohydrate; 2′,7′-dichlorodihydro-fluorescein diacetate; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium, MTT; BBB; DCFH-DA; DIV; DMEM; DMSO; Dulbecco’s Modified Eagle Medium; FJB; HI; HIE; LDH; MTT; NB; NS; OGD; PFA; ROS; TTC; blood–brain barrier; days in vitro; dimethyl sulfoxide; fluoro-jade B; hesperidin; hypoxia–ischemia encephalopathy; hypoxia–ischemic; hypoxia–ischemic encephalopathy; lactate dehydrogenase; neurobasal; normal saline; oxygen and glucose deprivation; paraformaldehyde; reactive oxygen species