4.6 Article

Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy

Journal

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 40, Issue 1, Pages 259-267

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2015.06.019

Keywords

Hepatic encephalopathy; Acute liver injury; Tranilast; Ammonia; Oxidative stress; Cytokines

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Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. (C) 2015 Elsevier B.V. All rights reserved.

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