Therapeutic role of telmisartan against acetaminophen hepatotoxicity in mice

Abstract

The therapeutic potential of telmisartan was investigated in mice exposed to acute hepatotoxicity induced by a single dose of acetaminophen (500 mg/kg, p.o.). Telmisartan treatment (two i.p. injections, 10 mg/kg, each) was given at 1 and 12 h following acetaminophen administration. Telmisartan significantly reduced the level of serum alanine aminotransferase, and suppressed lipid peroxidation, prevented the depletion of the antioxidant defenses (reduced glutathione level, and catalase and superoxide dismutase activities), and attenuated the elevation of nitric oxide resulted from acetaminophen administration. Also, telmisartan ameliorated the histopathological liver tissue damage induced by acetaminophen. Immunohistochemical analysis revealed that telmisartan significantly decreased the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue of mice received acetaminophen overdose. In conclusion, telmisartan can be considered as a potential therapeutic option to protect against acute acetaminophen hepatotoxicity commonly encountered in clinical practice. © 2012 Elsevier B.V. All rights reserved.