Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper Compounds

Abstract

Copper is an essential mineral and plays important roles in skin growth and activity. Copper delivery through skin can provide beneficial effects but its potential to induce skin irritation reactions is often overlooked. Data on dermal toxicity caused by copper compounds is scant. Some recognized in vitro skin toxicity methods are unsuitable for all metal compounds. Here, we employ a keratinocyte-based model and evaluated the skin irritation potential of copper compounds at cellular, genomic and proteomic levels. We determined cell viability and cytotoxicity by using tetrazolium reduction assay and Lactate Dehydrogenase (LDH) assay, performed real-time PCR and protein quantification to assess the expression of biomarkers after treating cells with copper peptide (GHK-Cu), copper chloride (CuCl2) and copper acetate (Cu(OAc)2). These copper compounds exhibited different irritancy potentials at the same treatment concentrations. GHK-Cu was not cytotoxic and did not induce any significant change in the expression levels of various skin irritation-related biomarkers. IL-1α and IL-8, HSPA1A and FOSL1 were significantly upregulated following 24-h treatment with CuCl2 and Cu(OAc)2 at 58 and 580 μM without concomitant inhibition in cell viability. GHK-Cu has a low potential of inducing skin irritation and therefore provides a safer alternative for the delivery of copper through skin.

Profiling of remote skeletal muscle gene changes resulting from stimulation of atopic dermatitis disease in NC/Nga mouse model

“…In addition, we showed that AD-related phenotype genes, Il18 , Il4ra , Il13ra1 , Tlr1 , Tlr7 , Tlr8 , Tlr13 , Fcer1a , Fcer2a , and Spink5l were upregulated in the microarray analysis [363738]. Hspa1a , Stat1 , Adam13 , and Adam23 were also upregulated and may be useful inflammatory markers [39404142]. We have also studied other genes considered to play integral roles in AD-like.…”

Effects of ivermectin and its combination with alpha lipoic acid on expression of IGFBP-3 and HSPA1 genes and male rat fertility

“…In our study, this gene was significantly upregulated in the group injected with ivermectin relative to control (Figure b). The HSP genes expression was induced under the physiopathological condition and by various stressful stimuli (Hunt et al., and Li et al., ). The induced expression of HSPA1A is needed for the refolding of damaged and unfolded proteins produced under stress (Scieglinska, Piglowski, Chekan, Mazurek, & Krawczyk, ).…”

Topical and nutricosmetic products for healthy hair and dermal antiaging using “dual‐acting” (2 for 1) plant‐based peptides, hormones, and cannabinoids

“…More importantly, GHK‐Cu has been shown to promote fibroblast proliferation together with the expression of ECM proteins and proteoglycans 21 . But unlike retinol, keratinocyte cells are modulated via a conservative orchestration of cellular signaling, with no significant change to interleukin‐1α expression 22 and moderate proliferation that is thought to derive from regulation of the epidermal extracellular matrix proteins, integrins α6 and β1. Integrin α6 is a marker of extracellular adhesion receptors common in the dermal‐epidermal junction.…”