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<p>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&#xa0;mg/kg, orally for seven consecutive days) on TAA (200&#xa0;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.</p> Graphical abstract <p>Mon, montelukast; TAA, thioacetamide; ALK-p, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LHD, lactate dehydrogenase; GGT, gamma-glutamyl transferase; SOD, superoxide dismutase; GS, reduced glutathione; MDA, malondialdehyde; ASK-1, apoptosis signal-regulating kinase 1; JNK, Jun N-terminal kinase; TNF-α, tumor necrosis factor-α; NF-κB, nuclear factor kappa B.</p> <p></p>

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Montelukast alleviates thioacetamide-induced hepatic encephalopathy in rats

  • 期刊论文

  • 发表日期：

    2025年5月24日

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  • Rehab S. Abdelrahman,
  • Rania R. Abdelaziz,
  • Marwa E. Abdelmageed

摘要

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.

Graphical abstract

Mon, montelukast; TAA, thioacetamide; ALK-p, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LHD, lactate dehydrogenase; GGT, gamma-glutamyl transferase; SOD, superoxide dismutase; GS, reduced glutathione; MDA, malondialdehyde; ASK-1, apoptosis signal-regulating kinase 1; JNK, Jun N-terminal kinase; TNF-α, tumor necrosis factor-α; NF-κB, nuclear factor kappa B.