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Liver toxicity assessments in rats following sub-chronic oral exposure to copper nanoparticles

Tang, Huaqiao, Xu, Min, Luo, Jie, Zhao, Ling, Ye, Gang, Shi, Fei, Lv, Cheng, Chen, Helin, Wang, Yanyan, Li, Yinglun
Environmental sciences Europe 2019 v.31 no.1 pp. 30
alanine transaminase, animal-based foods, aspartate transaminase, blood serum, copper, copper nanoparticles, dose response, feed additives, food safety, hepatotoxicity, histopathology, inflammation, ions, messenger RNA, mitogen-activated protein kinase, oral exposure, oxidative stress, pharmacokinetics, rats, receptors, respiratory system, risk, signal transduction, toxicity testing, transcription factor NF-kappa B
BACKGROUND: The widespread use of nano-copper as a feed additive in the absence of toxicological studies has potential risks to humans and animals. Toxicity studies on nano-copper in animals usually exposure from the respiratory tract, however, it is necessary to study the oral exposure toxicity of nano-copper to understand its risks as a feed additive. RESULTS: Currently the hepatotoxicity and mechanism of nano-copper after sub-choronic oral exposure at equivalent doses of 50, 100, and 200 mg/kg/day were evaluated in rats; micro-copper and Cu ions were used as controls. Nano-copper (200 mg/kg) increased serum alanine aminotransferase and aspartate aminotransferase significantly, further promoting hepatic oxidative stress, inflammation, and corresponding histopathological changes, and exhibited significant dose-dependent changes. Nano-copper also decreased the level of nuclear receptors, resulting in significant reductions in mRNA, protein, and activity of hepatic CYP450 enzymes. The molecular mechanisms responsible for these toxic effects involved the signaling pathway of NF-κB, MAPK, and STAT5. CONCLUSIONS: Nano-copper caused strong hepatic toxicity by inducing oxidative stress and inflammation. The decreased drug metabolism enzymes lead to nano-copper–drug interaction that provoked the concerns on animal-derived food safety.