title: 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 CuCl2and Cu(OAc)2at 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.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore.|3M Innovation Singapore, 100 Woodlands Avenue, 738205, Singapore.
authors.forename: Hairui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
authors.forename: Pei Zhen
authors.initials: PZ
authors.lastname: Toh
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
authors.forename: Jia Yao
authors.initials: JY
authors.lastname: Tan
authors.affiliation: 3M Innovation Singapore, 100 Woodlands Avenue, 738205, Singapore.
authors.forename: Melvin T
authors.initials: MT
authors.lastname: Zin
authors.affiliation: 3M Innovation Singapore, 100 Woodlands Avenue, 738205, Singapore.
authors.forename: Chi-Ying
authors.initials: CY
authors.lastname: Lee
authors.affiliation: 3M Innovation Singapore, 100 Woodlands Avenue, 738205, Singapore.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: 3M Innovation Singapore, 100 Woodlands Avenue, 738205, Singapore.
authors.forename: Melvina
authors.initials: M
authors.lastname: Leolukman
authors.affiliation: 3M Innovation Singapore, 100 Woodlands Avenue, 738205, Singapore.
authors.forename: Hongqian
authors.initials: H
authors.lastname: Bao
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Kang
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D003300:Copper; D007770:L-Lactate Dehydrogenase