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Exp Toxicol Pathol. 2013 Nov;65(7-8):1025-33. doi: 10.1016/j.etp.2013.03.001. Epub 2013 Apr 8.

Cytotoxicity evaluation and antioxidant enzyme expression related to heavy metals found in tuna by-products meal: An in vitro study in human and rat liver cell lines.

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Laboratory of Animal Ecophysiology, Sciences Faculty of Sfax, Department of Life Sciences, BP 1171, 3000 Sfax, Tunisia; Liver Research Facility/Labo Hepatology, University Hospital Gasthuisberg, Gebouw Onderwijs en Navorsing 1, bus 703, Herestraat 49, Leuven, Belgium. Electronic address:


Heavy metals can accumulate in organisms via various pathways, including respiration, adsorption and ingestion. They are known to generate free radicals and induce oxidative and/or nitrosative stress with depletion of anti-oxidants. Tuna by-product meal (TBM) is rich in proteins and can, therefore, offer an attractive protein source for animals. This study was undertaken to assess the effects of metals present in TBM, namely cadmium (Cd), lead (Pb), and mercury (Hg), separately or in combination with oxidative stress, on cell viability. Three cell models: rat liver FTO2B, human hepatoma HepG2, and human hepatic WRL-68, were used. Cell viability was determined following exposure to various concentrations of the metals. Two antioxidant genes, catalase (CAT) and superoxide dismutase (SOD), were measured to obtain a better understanding of oxidative stress-associated gene expression. Among the metals present in TBM, only Cd at a concentration of 30μM was noted to exhibit cytotoxic effects. This cytotoxicity was even more pronounced after co-stimulation with H2O2, used to mimic systemic oxidative stress. At non-toxic concentrations, Hg and Pb were noted to aggravate oxidative stress toxicity. The results further revealed that exposure to Cd, Pb, and a co-stimulation of H2O2 with Hg resulted in the increased expression of antioxidant gene SOD. A risk assessment of toxic contaminants in TBM indicated that food safety objectives should consider the human health impacts of foods derived from animals fed on contaminated meal and that much care should be taken when TBM is used in animal diet.


CAT; Cd; Cu; FM; FTO2B; Food toxicity; GAPDH; GPx; H(2)O(2); Heavy metal; HepG2; Hg; In vitro cytotoxicity; Mn; OD; Oxidative stress; Pb; ROS; SOD; TBM; Tuna by-product meal; WRL-68; cadmium; catalase; copper; fish meal; glutathione peroxidase; glyceraldehydes-3 phosphate dehydrogenase; human embryonic liver cell line; human liver cell line; hydrogen peroxide; lead; mRNA; manganese; mercury; messenger RNA; optical density; rat liver cell line; reactive oxygen species; superoxide dismutase; tuna by-product meal

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