The Effects of Chronic Iron Overload in Rats with Acute Acetaminophen Overdose

Zvi Ackerman*, Galina Skarzinski, Gabriela Link, Maya Glazer, Orit Pappo, Maria Grozovski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageAmerican English
Pages (from-to)597-607
Number of pages11
JournalToxicologic Pathology
Volume46
Issue number5
DOIs
StatePublished - 1 Jul 2018

Bibliographical note

Publisher Copyright:
© The Author(s) 2018.

Keywords

  • acetaminophen
  • hepatocellular and sinusoidal cell iron overload
  • metallothionein
  • nitrotyrosine
  • oxidative/antioxidative milieu

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