Nickel Nanoparticles Induced Hepatotoxicity in Mice via Lipid-Metabolism-Dysfunction-Regulated Inflammatory Injury

Abstract

Nickel nanoparticles (NiNPs) have wide applications in industry and biomedicine due to their unique characteristics. The liver is the major organ responsible for nutrient metabolism, exogenous substance detoxification and biotransformation of medicines containing nanoparticles. Hence, it is urgent to further understand the principles and potential mechanisms of hepatic effects on NiNPs administration. In this study, we explored the liver impacts in male C57/BL6 mice through intraperitoneal injection with NiNPs at doses of 10, 20 and 40 mg/kg/day for 7 and 28 days. The results showed that NiNPs treatment increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and induced pathological changes in liver tissues. Moreover, hepatic triglyceride (TG) content and lipid droplet deposition identified via de novo lipogenesis (DNL) progression were enhanced after NiNPs injection. Additionally, sustained NiNPs exposure induced a remarkable hepatic inflammatory response, significantly promoted endoplasmic reticulum stress (ER stress) sensors Ire1α, Perk and Atf6, and activated the occurrence of liver cell apoptosis. Overall, the research indicated that NiNPs exposure induced liver injury and disturbance of lipid metabolism. These findings revealed the public hazard from extreme exposure to NiNPs and provided new information on biological toxicity and biosafety evaluation.

Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms

“…The key role played by lipids in tissue physiology and cell signaling has been demonstrated in several studies [ 46 ], which have shown that abnormal changes in lipid metabolism can lead to cellular dysfunction and necrosis, resulting in cell death. Disorders of lipid metabolism are a key factor contributing to hepatotoxic injury [ 47 , 48 ]. Glycerophospholipid is an amphiphilic molecule that is directly involved in cellular physiological functions and helps transport triacylglycerol.…”