Carbon tetrachloride-induced lethality in mouse is prevented by multiple pretreatment with zinc sulfate

The Journal of Toxicological Sciences
Hiroki YoshiokaS Onosaka

Abstract

Carbon tetrachloride (CCl4) is commonly used as a chemical inducer of experimental liver injury. Several compounds have been demonstrated to attenuate the hepatic damage caused by sublethal doses of CCl4. However, rescue from lethal toxicity of CCl4 has not been reported. In the present study, we evaluated the protective effect of metallothionein (MT), an endogenous scavenger of free radicals, on CCl4-induced lethal toxicity of mice. To induce MT production in male ddY mice, we administered Zn (as ZnSO4) at 50 mg/kg as a once-daily subcutaneous injection for 3 days prior to a single intraperitoneal administration of 4 g/kg CCl4. Animals were observed for mortality every 3 hr for 24 hr after CCl4 injection. Liver damage was assessed by determining (in a subset of these mice) blood levels of alanine aminotransferase (ALT; a marker of liver injury) and liver histopathology at 6 hr after CCl4 injection. Our results showed that three times pretreatment with Zn yielded > 40-fold induction of hepatic MT protein levels compared to control group. Zn pretreatment completely abolished the CCl4-induced mortality of mice. We also found that pretreatment of mice with Zn significantly decreased the ALT levels and reduced the histological live...Continue Reading

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Citations

Jun 3, 2016·Biological & Pharmaceutical Bulletin·Hiroki YoshiokaSatomi Onosaka
Jun 9, 2016·Chemico-biological Interactions·Hiroki YoshiokaSatomi Onosaka
Sep 2, 2016·Biological & Pharmaceutical Bulletin·Hiroki YoshiokaAkito Nagatsu
Oct 7, 2016·Environmental Health and Preventive Medicine·Hiroki YoshiokaAkito Nagatsu
Oct 16, 2016·Environmental Health and Preventive Medicine·Hiroki YoshiokaTsunemasa Nonogaki
Mar 23, 2017·The Journal of Toxicological Sciences·Hiroki YoshiokaNobuhiko Miura
Oct 20, 2018·Biomedical Research·Hiroki YoshiokaYutaka Aoyagi
Nov 23, 2017·Environmental Health and Preventive Medicine·Hiroki YoshiokaTsunemasa Nonogaki
May 13, 2017·The Journal of Toxicological Sciences·Nobuhiko MiuraGi-Wook Hwang
Feb 27, 2018·The Journal of Toxicological Sciences·Hiroki YoshiokaNobuhiko Miura
Sep 5, 2017·Biological & Pharmaceutical Bulletin·Shiori FukayaSatomi Onosaka
Oct 17, 2018·Environmental Health and Preventive Medicine·Hiroki YoshiokaMakoto Nakao

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