Cilostazol Counteracts Mitochondrial Dysfunction in Hepatic Encephalopathy Rat Model: Insights into the role of cAMP/AMPK/SIRT1/ PINK-1/Parkin hub and p-CREB /BDNF/ TrkB neuroprotective trajectory

• Published in: European journal of pharmacology 2024-12, Vol.987, p.177194, Article 177194
• Main Authors: Gad, Enas S., Aldossary, Sara A., El-Ansary, Mona R., Abd El-Galil, Mona M., Abd-El-Hamid, Asmaa Hassan, El-Ansary, Amira R., Hassan, Noha F.
• Format: Article
• Language: English
• Subjects: AMPK/SIRT-1; Cilostazol; Hepatic encephalopathy; Oxidative stress; PINK -1/Parkin; Thioacetamide
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2024.177194

A devasting stage of chronic hepatic dysfunction is strictly correlated with neurological impairment, signifying hepatic encephalopathy (HE). HE is a multifactorial condition; therefore, hyperammonemia, oxidative stress, neuroinflammation, and mitochondrial dysfunction interplay in HE's progressive development. Cilostazol (Clio) has shown promising neuroprotective and hepatoprotective effectiveness in different neuronal and hepatic disorders; however, its efficiency against HE hasn't yet been explored. This study aimed to investigate the protective role of Cilo against thioacetamide (TAA)-induced HE in rats targeting mitochondrial dysfunction via modulation of Adenosine monophosphate-activated protein kinase (AMPK)/ Silent information regulator 1 (SIRT1) dependent pathways. Rats were allocated into three groups: the normal control group, the TAA group received (100 mg/kg, three times per week, for six weeks) to induce HE, and the Cilo group received (Cilo 100 mg/kg/day for six weeks, oral gavage) concurrently with TAA. Cilo counteracted HE indicated in the enhancement of cognitive impairment and the motor performance of rats (P