Calcium-deficient diet attenuates carbon tetrachloride-induced hepatotoxicity in mice through suppression of lipid peroxidation and inflammatory response.

Hiroki Yoshioka,Satomi Onosaka,Nobuyuki Fukuishi,Tsunemasa Nonogaki

doi:10.1016/j.heliyon.2016.e00126

Hiroki Yoshioka, Satomi Onosaka + Show 2 more

Open Access

https://doi.org/10.1016/j.heliyon.2016.e00126

Copy DOI

Journal: Heliyon	Publication Date: Jun 1, 2016
Citations: 30	License type: cc-by

Affiliation: Kinjo Gakuin University, Kobe Gakuin University

Abstract

The aim of this study is to investigate whether a Ca-deficient diet has an attenuating effect on carbon tetrachloride (CCl4)-induced hepatotoxicity. Four-week-old male ddY mice were fed a Ca-deficient diet for 4 weeks as a part of the experimental protocol. While hypocalcemia was observed, there was no significant change in body weight. The CCl4-exposed hypocalcemic mice exhibited a significant decrease in alanine aminotransferase and aspartate aminotransferase activities at both 6 h and 24 h even though markers of renal function remained unchanged. Moreover, lipid peroxidation was impaired and total antioxidant power was partially recovered in the liver. Studies conducted in parallel with the biochemical analysis revealed that hepatic histopathological damage was attenuated 24 h post CCl4 injection in hypocalcemic mice fed the Ca-deficient diet. Finally, this diet impaired CCl4-induced inflammatory responses. Although upregulation of Ca concentration is a known indicator of terminal progression to cell death in the liver, these results suggest that Ca is also involved in other phases of CCl4-induced hepatotoxicity, via regulation of oxidative stress and inflammatory responses.

Highlights

Carbon tetrachloride (CCl4) is widely used in experimental animal models that are meant to mimic human hepatotoxicity
The third step involves the overexpression of these free radicals leading to several deleterious effects such as enhanced membrane lipid peroxidation, covalent binding to macromolecules, ATP depletion, generation of inflammatory cytokines, and loss of Ca homeostasis [6, 7, 8]
To determine how CCl4-induced toxicity is impaired under hypocalcemic conditions, we examined hepatic injury markers ALT and AST, whose activities increase in CCl4-induced toxicity

Summary

Introduction

Carbon tetrachloride (CCl4) is widely used in experimental animal models that are meant to mimic human hepatotoxicity. The mechanism of CCl4 hepatotoxicity has been thoroughly studied since the 1970s, by using in vivo models of acute and chronic CCl4 poisoning, perfused livers, and isolated or cultured hepatocytes [1, 2]. The second step is radical binding; the free radicals react with antioxidant enzymes and sulfhydryl groups such as those in glutathione (GSH) and the protein thiol. The third step involves the overexpression of these free radicals leading to several deleterious effects such as enhanced membrane lipid peroxidation, covalent binding to macromolecules, ATP depletion, generation of inflammatory cytokines, and loss of Ca homeostasis [6, 7, 8]. Since sulfhydryl groups are essential elements of the molecular arrangement responsible for the Ca transport access cellular membranes, loss of these proteins inhibits microsomal and mitochondrial regulation of cellular Ca levels

Objectives

Methods

Results

Conclusion