Allergenicity and Bioavailability of Nickel Nanoparticles Compared to Nickel Microparticles in Mice

Abstract

Metal allergy is a common disease that afflicts many people. Nevertheless, the mechanism underlying metal allergy development has not been completely elucidated. Metal nanoparticles might be involved in the development of a metal allergy, but the associated details are unknown. In this study, we evaluated the pharmacokinetics and allergenicity of nickel nanoparticles (Ni-NPs) compared with those of nickel microparticles (Ni-MPs) and nickel ions. After characterizing each particle, the particles were suspended in phosphate-buffered saline and sonicated to prepare a dispersion. We assumed the presence of nickel ions for each particle dispersion and positive control and orally administered nickel chloride to BALB/c mice repeatedly for 28 days. Results showed that compared with those in the Ni-MP administration group (MP group), the Ni-NP administration group (NP group) showed intestinal epithelial tissue damage, elevated serum interleukin (IL)-17 and IL-1β levels, and higher nickel accumulation in the liver and kidney. Additionally, transmission electron microscopy confirmed the accumulation of Ni-NPs in the livers of both the NP and nickel ion administration groups. Furthermore, we intraperitoneally administered a mixed solution of each particle dispersion and lipopolysaccharide to mice and then intradermally administered nickel chloride solution to the auricle after 7 days. Swelling of the auricle was observed in both the NP and MP groups, and an allergic reaction to nickel was induced. Particularly in the NP group, significant lymphocytic infiltration into the auricular tissue was observed, and serum IL-6 and IL-17 levels were increased. The results of this study showed that in mice, Ni-NP accumulation in each tissue was increased after oral administration and toxicity was enhanced, as compared to those with Ni-MPs. Orally administered nickel ions transformed into nanoparticles with a crystalline structure and accumulated in tissues. Furthermore, Ni-NPs and Ni-MPs induced sensitization and nickel allergy reactions in the same manner as that with nickel ions, but Ni-NPs induced stronger sensitization. Additionally, the involvement of Th17 cells was suspected in Ni-NP-induced toxicity and allergic reactions. In conclusion, oral exposure to Ni-NPs results in more serious biotoxicity and accumulation in tissues than Ni-MPs, suggesting that the probability of developing an allergy might increase.

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

“…On the contrary, the combustion of nickel-containing fossil fuels, nickel-manufacturing industries and the utilization of nickel products has induced the excessive release of nickel compounds and nanoparticles into the environment, leading to hazardous health effects on organisms [39,40]. Previous studies have demonstrated that nickel nanoparticles have more intense toxicity and stronger sensitization than microparticles [29,41]. The liver is the major biological filtration barrier organ responsible for the sequestration and biodegradation of exogenous substances, medicines and nanomaterials [37].…”

“…NiNPs in the bloodstream are mainly detained by the liver [27][28][29]. Recent reports indicated that nickel and nickel-containing nanoparticles exhibited liver injury in vivo and in vitro.…”

Nano-based formulations of curcumin: elucidating the potential benefits and future prospects in skin cancer

“…For instance, nickel NPs have been shown to cause hypersensitivity reactions. On subsequent exposures, the body reacts more strongly, leading to severe inflammation and other allergic symptoms [136].…”