Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Original Article
Zinc sulfate pretreatment prevents carbon tetrachloride-induced lethal toxicity through metallothionein-mediated suppression of lipid peroxidation in mice
Hiroki YoshiokaSatomi Onosaka
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JOURNALS FREE ACCESS

2016 Volume 3 Issue 4 Pages 151-156

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Abstract

Carbon tetrachloride (CCl4) is a well-known hepatotoxic chemical. Exposure to CCl4 produces free radicals, which induce oxidative stress and cause hepatic injury. We demonstrated previously that pretreatment with zinc (Zn), which induces metallothionein (MT) expression, prevents CCl4-induced lethal toxicity in a dose-dependent manner. While MT has been suggested as a possible hepatoprotective protein, its mechanism of protection remains unknown. In the current study, we evaluated the protective mechanism of MT, an endogenous scavenger of free radicals, against CCl4-induced toxicity through subcutaneous administration of 50 mg/kg Zn (as ZnSO4) once daily for three consecutive days, prior to a single intraperitoneal injection of 4 g/kg CCl4 in male ddY mice. Our results showed that Zn pretreatment significantly decreased aspartate aminotransferase and total cholesterol levels, 6-hr after CCl4 injection, as well as lipid peroxidation. Moreover, CCl4-induced hepatic calcium level was downregulated by pretreatment with Zn while Zn-induced MT expression decreased by more than 500 µg/g liver (43%) in the Zn + CCl4-treated group, implying that MT was consumed by CCl4-induced free radicals. These findings suggest that prophylaxis with Zn protects mice from CCl4-induced acute hepatotoxicity, presumably by inducing the expression of free radical-scavenging MT.

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© 2016 The Japanese Society of Toxicology
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