title: The effect of acetaminophen nanoparticles on liver toxicity in a rat model.
abstract: Acetaminophen, a pain-reliever, is one of the most widely used medications in the world. Acetaminophen with normal dosage is considered a nontoxic drug for therapeutic applications, but when taken at overdose levels it produces liver damage in human and various animal species. By a high energy mechanically activated method, we produced acetaminophen in a nanometer crystalline size (24 nm). Forty-eight hours after injection of crystalline particles with normal and reduced size of our drug, the effect of liver toxicity was compared by determination of liver transferase enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase (ALT). These enzymes were examined by routine colorimetric methods using commercial kits and pathologic investigations. Statistical analysis and pathological figures indicated that ALT delivery and toxicity in reduced size acetaminophen was significantly reduced when compared with normal size acetaminophen. Pathology figures exhibited reduced necrosis effects, especially the confluent necrosis, in the central part of the lobule in the reduced size acetaminophen samples when compared with the normal samples.
authors.affiliation: Department of Chemistry, Islamic Azad University, Tonekabon Branch, Mazandaran, Iran. e.biazar@tonekaboniau.ac.ir
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Biazar
authors.forename: S Mahdi
authors.initials: SM
authors.lastname: Rezayat
authors.forename: Naser
authors.initials: N
authors.lastname: Montazeri
authors.forename: Khalil
authors.initials: K
authors.lastname: Pourshamsian
authors.forename: Reza
authors.initials: R
authors.lastname: Zeinali
authors.forename: Azadeh
authors.initials: A
authors.lastname: Asefnejad
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rahimi
authors.forename: Mohammadmajid
authors.initials: M
authors.lastname: Zadehzare
authors.forename: Mehran
authors.initials: M
authors.lastname: Mahmoudi
authors.forename: Rohollah
authors.initials: R
authors.lastname: Mazinani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ziaei
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D053758:Nanoparticles / Q000633:toxicity*; D051381:Rats
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
references.citation: Eur J Pharm Biopharm. 2003 Nov;56(3):393-400
references.pmid: 14602182
references.citation: Pharm Res. 2003 Dec;20(12):1917-25
references.pmid: 14725354
references.citation: Pharm Res. 1985 Nov;2(6):302-6
references.pmid: 24271128
references.citation: J Pharm Sci. 2003 Oct;92(10):2057-68
references.pmid: 14502544
references.citation: Eur J Clin Pharmacol. 1979 Jul;15(6):427-31
references.pmid: 499292
references.citation: Nat Rev Drug Discov. 2004 Sep;3(9):785-96
references.pmid: 15340388
references.citation: J Immunol. 2007 Mar 15;178(6):3777-85
references.pmid: 17339476
references.citation: Drug Metab Dispos. 2003 Dec;31(12):1499-506
references.pmid: 14625346