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Liver Toxicity of Thioacetamide is Increased by Hepatocellular Iron Overload

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Abstract

An increase in hepatic iron concentration might exacerbate liver injury. However, it is unknown whether hepatic iron overload may exacerbate acute liver injury from various toxins. Therefore, we evaluated how manipulations to increase hepatic iron concentration affected the extent of acute liver injury from thioacetamide. In this study, we used rats with either “normal” or increased hepatic iron concentration. Iron overload was induced by either providing excess iron in the diet or by injecting iron subcutaneously. Both routes of providing excess iron induced an increase in hepatic iron overload. Meanwhile, the subcutaneous route induced both hepatocellular and sinusoidal cell iron deposition; the oral route induced lesser degree of hepatic iron concentration and only hepatocellular iron overload. Thioacetamide administration to the rats with “normal” hepatic iron concentration induced hepatic cell necrosis and apoptosis associated with a remarkable increase in serum aminotransaminases and depletion of hepatic glutathione and other antioxidative indices. Thioacetamide administration to the iron-overloaded rats exacerbated the extent of liver injury only in the rats orally induced with iron overload. In the rats subcutaneously induced with iron overload, the extent of liver injury from thioacetamide was not different from that observed in the rats with “normal” iron overload. It was concluded that the outcome of thioacetamide-induced acute liver injury may depend on both the level of hepatic iron concentration and on the cellular distribution of iron. While isolated hepatocellular iron overload may exacerbate thioacetamide-induced acute liver injury, a combined hepatocellular and sinusoidal cell iron deposition, even at high hepatic iron concentration, had no such an effect.

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Authors and Affiliations

  1. Department of Medicine, Hadassah-Hebrew University Medical Center, Mount Scopus Campus, P.O. Box 24035, 91240, Jerusalem, Israel

    Zvi Ackerman & Maya Glazer

  2. Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Orit Pappo

  3. Department of Human Nutrition and Metabolism, Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Gabriela Link

  4. Biotechnology Department, Ort Braude College of Engineering, Karmiel, Israel

    Maria Grozovski

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  1. Zvi Ackerman
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  2. Orit Pappo
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  3. Maya Glazer
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  4. Maria Grozovski
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Correspondence to Zvi Ackerman.

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Ackerman, Z., Pappo, O., Link, G. et al. Liver Toxicity of Thioacetamide is Increased by Hepatocellular Iron Overload. Biol Trace Elem Res 163, 169–176 (2015). https://doi.org/10.1007/s12011-014-0110-9

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  • DOI: https://doi.org/10.1007/s12011-014-0110-9

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