Immunohistochemical localization of afatinib in male rat intestines and skin after its oral administration |
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| Affiliation: | 1. Applied Life Science Department, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan;2. Department of Pharmacy, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan;3. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, 849-8501, Japan;1. University of Ottawa, Institute of Mental Health Research, Ottawa, ON, Canada;2. School of Psychology, University of Ottawa, Ottawa, ON, Canada;3. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada;4. Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada;1. Department of Pharmacy, Akita University Hospital, Akita, Japan;2. Department of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, Akita, Japan;1. Cátedra CONACYT – Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Autónoma de México, CDMX, Mexico;2. Laboratorio Nacional de Canalopatías, Universidad Nacional Autónoma de México, CDMX, Mexico;3. PE en Química Clínica, Facultad de Ciencias de la Salud, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico;4. Departamento de Neurofisiología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, Mexico;5. Centro de Investigación en Genética y Ambiente, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico;1. Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan;2. Department of Neurology, Hiroshima City Asa Hospital, Hiroshima, Japan;1. Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan;2. Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan;1. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China;2. Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, China;3. Peking University Third Hospital Yanqing Hospital, Beijing, China |
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| Abstract: | Afatinib, a second-generation tyrosine kinase inhibitor, was designed to bind covalently to and irreversibly inhibit active ErbB family receptors. The major metabolites of afatinib in human plasma are adducts of afatinib covalently bound to plasma proteins via. the Michael addition reaction. These findings suggest that afatinib may form covalent bonds with proteins in tissue and be localized in tissue. However, there is no method for the specific detection of afatinib-protein conjugates localized in tissue. In this paper, we aimed to develop an immunohistochemical protocol to detect afatinib-protein conjugates. Immunostainings were performed with male rat intestinal tract and skin at 24 h after an oral administration of afatinib. In the intestinal tract, strong staining was observed in the ileum and colon, but only slight staining was observed in the duodenum and jejunum. In the skin, strong staining was observed in the epidermis, sebaceous glands and hair follicles. Immunohistochemistry for afatinib-protein conjugates could be a useful tool to detect the localization of such conjugates. This study is the first to elucidate the localization of afatinib-protein conjugates in the rat intestinal tract and skin and is expected to be of great use in efforts to clarify the mechanism underlying afatinib-induced diarrhoea or skin toxicities. |
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| Keywords: | Afatinib Immunohistochemistry Intestine Skin Localization |
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