Original StudyAluminum Chloride–Induced Apoptosis Leads to Keratinization Arrest and Granular ParakeratosisFujii, Mizue MD, PhD*; Kishibe, Mari MD, PhD*; Honma, Masaru MD, PhD*; Anan, Takashi MD, PhD†; Ishida-Yamamoto, Akemi MD, PhD†Author Information *Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan; and †Sapporo Dermatopathology Institute, Sapporo, Japan. Correspondence: Mizue Fujii, Department of Dermatology, Asahikawa Medical University, Asahikawa 078-8510, Japan (e-mail: [email protected]). The authors declare no conflicts of interest. The American Journal of Dermatopathology: October 2020 - Volume 42 - Issue 10 - p 756-761 doi: 10.1097/DAD.0000000000001513 Buy Metrics Abstract Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.