Reduction of Hepatotoxicity Induced by Acetaminophen Overdoses in a Mouse Model of Inflammation Induced by Freund's Adjuvants
- *Corresponding Author:
- Alexander Batista Duharte
Immunotoxicology Laboratory, Toxicology and Biomedicine Center (TOXIMED)
Medical Sciences University, P.O. Box 4033 National Highway
Km 1 1/2. Santiago de Cuba Cuba
Tel: 532264 3796, 5322643926
Fax: 5322643864, 5322687188
E-mail: [email protected]
Received date: June 05, 2014; Accepted date: July 11, 2014; Published date: July 18, 2014
Citation: García NP, Lores OF, Fuentes DP, Martínez DT, Hernandez JB, et al. (2014) Reduction of Hepatotoxicity Induced by Acetaminophen Overdoses in a Mouse Model of Inflammation Induced by Freund´s Adjuvants. J Allergy Ther 5:183. doi: 10.4172/2155-6121.1000183
Copyright: © 2014 García NP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acetaminophen (APAP) is often used as an analgesic and antipyretic during the inflammatory process. Its toxicity in overdoses depends on the integrity of the hepatic cytochrome P450 (CYP). The oxidative drug metabolism mediated by CYP can be inhibited during inflammatory diseases or after use of immuno-stimulants drugs and vaccines. The objective of this work was to evaluate if inflammation is able to modulate the toxicity of APAP. Five female Balb/c mice were injected subcutaneously with Freund Complete Adjuvant (FCA), and boosted with Freund’s Incomplete Adjuvant (FIA) at 14th day. Then, they were treated with 360 mg/kg of acetaminophen orally during the 14th, 15th and 16th days. Convenient control groups were included with APAP administration without immuno-stimulation. Serum levels of IL-1β, TNFα, IFNγ, α-1-acid glycoprotein (α-1-AGP), alanine transaminase (ALT), aspartic acid aminotransferase (AST), lactate dehydrogenase (LDH) and hepatic CYP2E1 expression were measured. Inoculation site of adjuvants and liver histopathological responses were also evaluated. FCA/FIA injection produced acute inflammatory response in the inoculation site and increased serum levels of the pro-inflammatory cytokines, α-1-AGP and LDH with reduction of hepatic CYP2E1 expression. A reduction of liver damage induced by APAP overdoses was also observed, suggesting that inflammatory processes can be protective against APAP hepatotoxicity.