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Naringenin mitigates thioacetamide-induced hepatic encephalopathy in rats: targeting the JNK/Bax/caspase-8 apoptotic pathway

Hepatic encephalopathy (HE) is a serious neurological disorder which is related to liver dysfunction. HE was induced by thioacetamide (TAA) injection (350 mg kg −1 , i.p.) for 3 consecutive days. This study was performed to investigate the prophylactic impact of naringenin against TAA-induced HE. Na...

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Bibliographic Details
Published in:Food & function 2023-01, Vol.14 (2), p.1248-1258
Main Authors: Eraky, Salma M, El-Kashef, Dalia H, El-Sherbiny, Mohamed, Abo El-Magd, Nada F
Format: Article
Language:English
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Summary:Hepatic encephalopathy (HE) is a serious neurological disorder which is related to liver dysfunction. HE was induced by thioacetamide (TAA) injection (350 mg kg −1 , i.p.) for 3 consecutive days. This study was performed to investigate the prophylactic impact of naringenin against TAA-induced HE. Naringenin (100 mg kg −1 ) was orally administered for 7 days starting 4 days prior to TAA injection. Naringenin effectively mitigated TAA-induced behavioural, structural and functional alterations. Naringenin ameliorated TAA-induced cognitive impairment as evidenced by the increase in the fall-off time in the rotarod test, decrease in the escape latency in the Morris water maze test and increase in the time spent in the center and in the number of rearing in the open field test. Additionally, naringenin significantly decreased the serum levels of transaminases, alkaline phosphatase, gamma-glutamyl transferase, bile and ammonia. Moreover, naringenin succeeded in reducing the levels of hepatic and cerebral c-Jun N-terminal kinases (JNK) as well as hepatic SORT1 levels. In addition, naringenin successfully elevated the levels of hepatic and cerebral pro-brain-derived neurotrophic factor (pro-BDNF) and BDNF in addition to the cerebral SORT1 level. Finally, naringenin markedly decreased the expression of Bax and caspase-8 as presented by the immunohistochemical results. Collectively, the ameliorative effect of naringenin on the development of HE might be attributed to the modulation of the JNK/Bax/caspase-8 apoptotic pathway. The proposed mechanism of naringenin (NGN) in reversing thioacetamide inducing hepatic encephalopathy through its anti-apoptotic properties through upregulation of pro-BDNF, BDNF and down-regulation of cJNK/Bax/caspase-8 pathway.
ISSN:2042-6496
2042-650X
DOI:10.1039/d2fo03470k