BACKGROUND
Hesperidin (HPD) is a
bioflavonoid found in citrus fruits. This study aimed to investigate the effects of HPD on cerebral morphology and cognitive behavior in
sevoflurane anesthetized neonatal rats and the molecular mechanisms involved. MATERIAL AND METHODS Sixty neonatal Sprague-Dawley rats were divided into five groups, including the untreated control group, and the
sevoflurane anesthesia groups untreated and treated with 25 mg/kg/day of HPD (HPD25), 50 mg/kg/day of HPD (HPD50), and 100 mg/kg/day of HPD (HPD100). The rat model was created by the administration of
sevoflurane on the sixth postnatal day (P6) and for a further three days. Neonatal rats pre-treated with HPD for 19 days were given
sevoflurane 30 minutes beforehand (P3 to P21). Rat hippocampal tissue specimens were investigated using the TUNEL assay for apoptosis. Hippocampal tissue homogenates underwent Western blot for the quantification of markers of
neuroinflammation and oxidative stress. The neonatal rats were also investigated for behavior, learning, and memory. RESULTS HPD significantly reduced
sevoflurane-induced neuronal apoptosis and
protein expression of cleaved
caspase-3, BAD, BAX,
NF-kappaB,
TNF-alpha,
IL-6, and IL-1ß (p<0.05). HPD significantly increased the expression of Bcl-xL and Bcl-2 (p<0.05), and activated the PI3/Akt pathway. Learning and memory were significantly improved following HPD treatment (p<0.05). HPD treatment modulated the PI3/Akt/PTEN and
NF-kappaB signaling pathways, and reduced oxidative stress (p<0.05). CONCLUSIONS In the
sevoflurane anesthetized neonatal rat model, treatment with HPD reduced neuronal degeneration, hippocampal
inflammation, and improvised memory, learning, and cognitive responses by modulating the PI3/Akt/PTEN and
NF-kappaB signaling pathways.