title: 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, 10mg/kg, each) was given at 1 and 12h 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.
authors.affiliation: Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia. amrfouad65@yahoo.com
authors.forename: Amr A
authors.initials: AA
authors.lastname: Fouad
authors.forename: Abdulruhman S
authors.initials: AS
authors.lastname: Al-Mulhim
authors.forename: Iyad
authors.initials: I
authors.lastname: Jresat
authors.forename: Wafaey
authors.initials: W
authors.lastname: Gomaa
mesh_terms: D000082:Acetaminophen; D000410:Alanine Transaminase / Q000097:blood; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D000804:Angiotensin II; D009569:Nitric Oxide; D000082:Acetaminophen; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D005978:Glutathione; D000077333:Telmisartan