Weaning mice and adult mice exhibit differential carbon tetrachloride-induced acute hepatotoxicity

Tae Bin Jeong, Doyoung Kwon, Seung Won Son, Sou Hyun Kim, Yun Hee Lee, Min Soo Seo, Kil Soo Kim, Young Suk Jung

Research output: Contribution to journalArticle

Abstract

Age is a risk factor for drug-induced liver injury (DILI). However, there is a limited understanding of pediatric DILI. Here, 2-week-old weaning and 8-week-old adult male ICR mice were intraperitoneally injected with CCl4 (0.1 mmol/kg equal to 15.4 mg/kg) to comparatively evaluate the time-dependent liver damage and cellular events. CCl4 significantly enhanced the serum alanine aminotransferase/aspartate aminotransferase levels and hepatic centrilobular necrosis in the weaning mice, whereas it induced mild liver injury in the adult mice. CCl4-treated weaning mice exhibited higher hepatic levels of pro-apoptotic proteins (Bax, cleaved caspase-3,-7, and-9), activated MAPKs (p-JNK and p-Erk), and endoplasmic reticulum stress indicators (ATF6 and CHOP) and lower hepatic anti-apoptotic Bcl-2 levels than the adult mice. The weaning mice exhibited enhanced basal hepatic glutathione (GSH) levels due to high glutamate cysteine ligase (GCL) and low anti-cysteine dioxygenase (CDO) enzyme levels. However, CCl4 markedly reduced the hepatic GSH levels only in the weaning mice. Furthermore, higher hepatic levels of oxidative stress-induced malondialdehyde, 4-hydroxynonenal, nitrotyrosine-protein adducts, and oxidized proteins were observed in CCl4-treated weaning mice than in CCl4-treated adult mice. The enhanced levels of hepatic cytochrome P450 (CYP) 2E1 and CYP3A, and decreased hepatic GSH S-transferase (GST)-π and GSH reductase (GR) levels in the weaning mice may contribute to their enhanced susceptibility to liver damage.

Original languageEnglish
Article number201
JournalAntioxidants
Volume9
Issue number3
DOIs
Publication statusPublished - 2020 Mar

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Jeong, T. B., Kwon, D., Son, S. W., Kim, S. H., Lee, Y. H., Seo, M. S., Kim, K. S., & Jung, Y. S. (2020). Weaning mice and adult mice exhibit differential carbon tetrachloride-induced acute hepatotoxicity. Antioxidants, 9(3), [201]. https://doi.org/10.3390/antiox9030201