{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:44:22Z","timestamp":1765295062567,"version":"3.37.3"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"am","delay-in-days":366,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","award":["Unassigned"],"award-info":[{"award-number":["Unassigned"]}],"id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cadmium is a toxic metal contained in food, water and the atmosphere, and exposure to cadmium can cause respiratory diseases in humans. Various health problems caused by cadmium result from oxidative stress-dependent cellular injury. Metallothioneins are intracellular, cysteine-rich, metal-binding proteins that have a detoxifying action on heavy metals such as cadmium in various organs. In addition, expression of metallothioneins is induced by metals with low biological toxicity, such as zinc. Therefore, in this study we examined whether polaprezinc, a chelate compound consisting of carnosine and zinc, can suppress cadmium-induced lung epithelial cell death. We found that cell viability markers (intracellular ATP levels and mitochondrial activity) and cytotoxicity (lactate dehydrogenase release) were decreased and increased, respectively by cadmium treatment; however, polaprezinc significantly reversed these changes. Moreover, cadmium-dependent endoplasmic reticulum stress responses were suppressed by polaprezinc treatment. We then examined the protective mechanisms of polaprezinc, focusing on oxidative stress. Cadmium induced the production of reactive oxygen species (ROS) in A549 cells in a dose-dependent manner and polaprezinc significantly suppressed this cadmium-induced ROS production. Finally, we examined whether polaprezinc exerts an antioxidative action by inducing metallothioneins. We found that polaprezinc dose-dependently induced metallothioneins using real-time RT-PCR, ELISA, and western blotting analyses. These results indicate that polaprezinc can suppress cadmium-induced lung epithelial cell death and oxidative stress by inducing metallothioneins. We therefore suggest that polaprezinc may have therapeutic effects against respiratory diseases, such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.<\/jats:p>","DOI":"10.1039\/c9mt00060g","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T14:34:19Z","timestamp":1560954859000},"page":"1310-1320","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Protective effect of polaprezinc on cadmium-induced injury of lung epithelium"],"prefix":"10.1093","volume":"11","author":[{"given":"Kazuma","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukari","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshifumi","family":"Sugizaki","sequence":"additional","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikako","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahoko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-4235","authenticated-orcid":false,"given":"Masahiro","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-0751","authenticated-orcid":false,"given":"Ken-ichiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. Fax: +81-42-468-9335; Tel: +81-42-468-9335"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,6,19]]},"reference":[{"key":"2021121516075291100_cit1","first-page":"135","article-title":"Cadmium toxicity and treatment: an update","volume":"8","author":"Rafati Rahimzadeh","year":"2017","journal-title":"Caspian J. Intern. Med."},{"key":"2021121516075291100_cit2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0147-6513(83)90050-7","article-title":"Cadmium concentrations in tobacco and tobacco smoke","volume":"7","author":"Scherer","year":"1983","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2021121516075291100_cit3","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.envpol.2016.01.025","article-title":"Heavy metals in PM2.5 and in blood, and children's respiratory symptoms and asthma from an e-waste recycling area","volume":"210","author":"Zeng","year":"2016","journal-title":"Environ. 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