論文

査読有り
2017年4月

Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced hepatotoxicity through elevated oxidative stress in mice

PLOS ONE
  • Hiroki Yoshioka
  • ,
  • Haruki Usuda
  • ,
  • Nobuhiko Miura
  • ,
  • Nobuyuki Fukuishi
  • ,
  • Tsunemasa Nonogaki
  • ,
  • Satomi Onosaka

12
4
開始ページ
e0176524
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0176524
出版者・発行元
PUBLIC LIBRARY SCIENCE

The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4)-induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals with V.D3 caused further elevation of the values of these liver functional markers without altering kidney functional markers; continued weight loss; a lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on plasma markers of liver or kidney damage or on total antioxidant power or lipid peroxidation. The potentiating effect of V.D3 was positively correlated with elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia transiently (within 3 h of injection), our results suggest that calcium enhances the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative stress.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0176524
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28448545
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000400383600095&DestApp=WOS_CPL