Hepatoprotective effect of amifostine and WR-1065 on acetaminophen-induced liver toxicity on Wistar rats.

Autor: Rasouli H; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran., Razavi BM; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.; Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran., Ghasemzadeh Rahbardar M; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran., Sadeghian H; Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran., Tabatabaee Yazdi SA; Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran., Hosseinzadeh H; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. hosseinzadehh@mums.ac.ir.; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. hosseinzadehh@mums.ac.ir.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Aug; Vol. 397 (8), pp. 6001-6015. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1007/s00210-024-03000-2
Abstrakt: Purpose: The most important problem with acetaminophen is its hepatotoxicity. N-acetylcysteine (NAC) is used to treat the hepatotoxicity of acetaminophen. Due to the structural similarities of this compound with amifostine, we decided to test the effect of this substance and its metabolite, WR-1065, on the hepatotoxicity of acetaminophen.
Methods: The single-dose method contained 1. Control; 2. Acetaminophen (1 g/kg, gavage); 3-5. Acetaminophen + amifostine (100, 200, 400 mg/kg, i.p.); 6-8. Acetaminophen + WR-1065 (50, 100, 200 mg/kg, i.p.); and 9. Acetaminophen + NAC (100, 200 mg/kg, i.p.). The multiple-dose method included the same groups: amifostine (50, 100, 200 mg/kg), WR-1065 (25, 50, 100 mg/kg), and NAC (100 mg/kg). Then, animals were sacrificed, and blood samples were collected for measuring ALT, AST, ALP, and T-Bil, liver tissue for histopathological examination, MDA, and GSH amounts.
Results: Acetaminophen increased the levels of MDA, T-Bil, ALT, AST, and ALP, decreased GSH levels, and augmented necrosis, neutrophils, lymphocytes, and macrophages in the port space in single-dose and multiple-dose studies. Amifostine and WR-1065 significantly reduced the levels of MDA, T-Bil, ALT, AST, ALP, increased GSH content, and ameliorated histopathological alterations in a single-dose and multiple-dose method compared to the acetaminophen group. Moreover, NAC caused a significant decrease in the levels of MDA, T-Bil, ALT, AST, and ALP, and reduced GSH amounts in single-dose and multiple-dose studies.
Conclusion: Amifostine and WR-1065 as antioxidant and hepatoprotective compounds are effective in reducing acetaminophen-induced hepatotoxicity with a similar effect to NAC and can be administered as an adjunct in the treatment of acetaminophen overdose.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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