The Effects of Chronic Iron Overload in Rats with Acute Acetaminophen Overdose. (July 2018)

• Record Type: Journal Article
• Authors: Ackerman, Zvi; Skarzinski, Galina; Link, Gabriela; Glazer, Maya; Pappo, Orit; Grozovski, Maria
• Is Part Of: Toxicologic pathology. Volume 46:Number 5(2018)
• Page Start: 597
• Page End: 607
• Publication Date: 2018-07
• Subjects: acetaminophen -- hepatocellular and sinusoidal cell iron overload -- oxidative/antioxidative milieu -- metallothionein -- nitrotyrosine; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623318776887
• Languages: English
• ISSNs: 0192-6233

Abstract

Background and Aims: Rats are resistant to acetaminophen (APAP) hepatotoxicity. In this study, we evaluated whether by augmentation of the hepatic oxidative stress, through the induction of hepatic iron overload (IO), it will be feasible to overcome the resistance of rats to the toxic effects of APAP. Method: Rats with no or increased hepatic IO. Results: Providing iron by diet induced hepatocellular IO, while parenteral iron administration induced combined hepatocellular and sinusoidal cell IO. APAP administration to rats with no IO caused an increase in hepatic oxidative stress and a decrease in the hepatic antioxidative markers but no hepatic cell damage. APAP administration to rats with hepatocellular IO further amplified the hepatic oxidative stress but induced only hepatocyte feathery degeneration without any increase in serum aminotransaminases. APAP administration to rats with combined hepatocellular and sinusoidal cell IO caused an unexpected decrease in hepatic oxidative stress and increase in the hepatic antioxidative markers and no hepatic cell damage. No hepatic expression of activated c-jun-N-terminal kinase was detected in any of the rats. Conclusions: The hepatic distribution of iron may affect its oxidative/antioxidative milieu. Augmentation of hepatic oxidative stress did not increase the rats' vulnerability to APAP.