Analysis of Nickel Distribution by Synchrotron Radiation X-ray Fluorescence in Nickel-Induced Early- and Late-Phase Allergic Contact Dermatitis in Hartley Guinea Pigs
Nickel-induced allergic contact dermatitis (Ni-ACD) is a significant global health issue, particularly prevalent in developed countries. Nickel, a common contact allergen, affects approximately 10% of women and 1-2% of men, primarily due to frequent exposure to nickel-containing jewelry. Despite regulatory efforts to limit nickel exposure, such as the European Union’s nickel restriction directive, up to 21% of market accessories still release nickel, and coins made of nickel alloys often exceed safe exposure thresholds. This ongoing exposure underscores the need for detailed research into the mechanisms of nickel-induced skin inflammation and the distribution of nickel within skin tissues.
The study aimed to investigate the penetration process and distribution of nickel in skin tissues during the early and late phases of Ni-ACD in Hartley guinea pigs. The research utilized synchrotron radiation micro X-ray fluorescence spectroscopy (SR-m-XRF) and micro X-ray absorption near-edge spectroscopy (m-XANES) to analyze the depth profile of nickel concentration in the skin and to understand the chemical state of nickel within the tissue.
Forty Hartley guinea pigs were divided into four groups based on the concentration of nickel sulfate (NiSO4) used for sensitization and challenge: the 5% NiSO4 group (5% sensitization, 10% challenge; late phase group), the 10% NiSO4 group (10% sensitization, 10% challenge; early phase group), and positive and negative control groups. The animals were sensitized by percutaneous application of NiSO4 solution to a shaved skin area on the left flank and challenged by occlusive patch tests on the right flank. Skin reactions, including erythema and swelling, were evaluated at various time points after the challenge.
Pathological biopsies were performed on each group, and the skin specimens were analyzed using SR-m-XRF and m-XANES. The SR-m-XRF experiments were conducted at the Beijing Synchrotron Radiation Facility (BSRF), where the incident X-ray energy was monochromatized at 15 keV and focused to a 50-micron diameter. The XANES experiments were performed at the 1W2B wiggler beamline of BSRF, where the micro-XANES spectra at the nickel K-edge were collected in fluorescence mode.
The results showed that the nickel element concentration in both the 5% NiSO4 group and the 10% NiSO4 group was significantly higher than that in the negative control group. In the early phase group, the nickel concentration was significantly higher in the upper 300-micron section of the skin compared to the lower section. In deeper sections (>200 microns), the nickel concentration in the early phase group was approximately equal to that in the late phase group. The SR-m-XRF data indicated that the nickel concentration in the late phase group was uniformly distributed, while in the early phase group, the nickel concentration peaked in the epidermis and decreased gradually with depth.
The XANES data revealed structural changes in the skin model sample compared to the 10% NiSO4 solution, indicating that nickel was not present in the Ni2+ aqueous ionic state but bound to nickel-binding proteins. This finding suggests that nickel forms complexes with certain proteins in the stratum corneum, which may play a role in the pathogenesis of Ni-ACD.
Histopathological analysis of the skin tissues showed that the late phase group exhibited features such as epidermal thickening, hyperkeratosis, parakeratosis, and acanthosis, as well as angiotelectasis and inflammatory cell infiltration in the epidermis and dermis. The early phase group showed more pronounced inflammatory cell infiltration in the dermis, along with intracellular edema, liquefaction, and denaturation of the basal layer.
The study concluded that the distribution of nickel in ACD skin tissue differs between the early and late phases. In the early phase, nickel is concentrated in the epidermis and penetrates to the dermis, while in the late phase, the nickel concentration is more uniformly distributed. The nickel element is not present in the Ni2+ aqueous ionic state but is bound to proteins, forming complexes in the stratum corneum. The use of SR-m-XRF and XANES technologies provided non-invasive, depth-resolved structural analysis of the skin tissues, offering valuable insights into the mechanisms of nickel-induced allergic contact dermatitis.
This research highlights the importance of understanding the penetration and distribution of haptens like nickel in the skin to develop effective strategies for preventing and treating Ni-ACD. The findings suggest that nickel-binding proteins in the stratum corneum may be key targets for therapeutic interventions. Further research is needed to identify the specific proteins involved in nickel binding and to explore their role in the immune response to nickel exposure.
The study also underscores the potential of synchrotron radiation techniques in dermatological research, providing detailed information on the spatial distribution and chemical state of metal allergens in skin tissues. These technologies could be applied to screen for metal-affected lesions and evaluate the effects of permeated metal elements on skin tissue lesions, contributing to the development of more precise diagnostic and therapeutic approaches for contact dermatitis.
In summary, this study provides valuable insights into the mechanisms of nickel-induced allergic contact dermatitis, demonstrating the differences in nickel distribution between the early and late phases of the disease. The findings highlight the role of nickel-binding proteins in the stratum corneum and the potential of synchrotron radiation techniques for non-invasive analysis of skin tissues. These results contribute to a better understanding of Ni-ACD and may inform the development of new strategies for its prevention and treatment.
doi.org/10.4103/0366-6999.233964
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