Montelukast alleviates thioacetamide-induced hepatic encephalopathy in rats

Hepatic encephalopathy (HE) is a serious neuropsychiatric dysfunction associated with acute and chronic liver disease. Montelukast (Mon) is a cysteinyl leukotriene receptor 1 (CysLT1R) antagonist approved as adjuvant therapy for asthma. The antioxidant and anti-inflammatory effects of montelukast have been reported in previous studies. To the best of our knowledge, Mon therapeutics' efficacy against thioacetamide-induced HE has not been investigated. This study aims to detect the protective effects of Mon (5 and 10 mg/kg, orally for seven consecutive days) on TAA (200 mg/kg, i.p., at three alternative days) induced HE in rats and to demonstrate its hepato/neuroprotective effects mechanisms. Results showed that Mon significantly improved hepatic and brain function, suppressed the release of inflammatory factors (brain and liver levels of NF-κB and TNF-α), and reduced oxidative stress (MDA and NO levels in both the brain and liver). Moreover, Mon activated PI3K/Akt expression in the brain and suppressed TAA-induced brain caspase-3 expression. Finally, TAA-induced histopathological changes in brain and liver sections were markedly normalized by Mon. Mon shows promise as a therapeutic agent in experimental HE models, and its mechanism of action involves the upregulation of PI3K/Akt expression, thereby inhibiting the expression of caspase-3 and the activity of TNF-α and NF-κB.