title: Skin toxicology of lead species evaluated by their permeability and proteomic profiles: a comparison of organic and inorganic lead.
abstract: Lead compounds are known to cause cytotoxicity and genotoxicity. Lead absorption by the skin is an important route through which this metal enters the body. The purpose of this work was to evaluate the skin permeability and toxicological profiles of two lead species, lead acetate and lead nitrate. This study assessed lead-induced toxicity mechanisms by focusing on the histopathology, proteomics, cell growth, and cellular ATP. In vitro skin permeation assays showed that there was no significant difference of lead accumulation within and across the skin between the two lead species. The presence of simulated sweat reduced the skin uptake of lead. The skin deposition of lead acetate was greater than that of lead nitrate with in vivo topical application. On the other hand, lead nitrate produced greater changes in the skin's histology and proteomic profiles compared to lead acetate. Four protein spots which showed significant changes were identified and are discussed in this study. These included glucose-related protein precursor (GRP) 78, K14, alpha-actin, and Rho GDP-dissociation inhibitor 2 (RhoGDI2). These proteins are respectively associated with oxidative stress, apoptosis, wound healing, and proliferation. Lead presented a biphasic pattern on cell growth and intracellular ATP content, with a stimulating effect at low concentrations and an inhibitory effect on cell proliferation at higher concentrations.
authors.affiliation: School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors.forename: Tai-Long
authors.initials: TL
authors.lastname: Pan
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Al-Suwayeh
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005347:Fibroblasts / Q000187:drug effects; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008819:Mice, Nude; D009566:Nitrates / Q000493:pharmacokinetics / Q000633:toxicity*; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D010539:Permeability; D011506:Proteins / Q000378:metabolism; D020543:Proteome; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D000199:Actins; D000091342:Endoplasmic Reticulum Chaperone BiP; D020730:Guanine Nucleotide Dissociation Inhibitors; D006360:Heat-Shock Proteins; D009566:Nitrates; D009942:Organometallic Compounds; D011506:Proteins; D020543:Proteome; D025521:Tumor Suppressor Proteins; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D007854:Lead; C017461:lead nitrate; C008261:lead acetate