{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:11:52Z","timestamp":1790021512580,"version":"4.0.1"},"reference-count":37,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Science and Technology Program of Zhejiang Province","award":["2022RC083 and 2022RC295"],"award-info":[{"award-number":["2022RC083 and 2022RC295"]}]},{"name":"Scientific Research Project of Taizhou Science and Technology Bureau in Zhejiang Province","award":["20ywa39, 20ywa45, and 20ywb66"],"award-info":[{"award-number":["20ywa39, 20ywa45, and 20ywb66"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Cadmium (Cd) is hazardous to human health because of its cytotoxicity and long biological half-life. Azoramide is a small molecular agent that targets the endoplasmic reticulum (ER) and moderates the unfolded protein response. However, its role in Cd-induced cytotoxicity remains unclear. This study was performed to investigate the protective effect of azoramide against Cd-induced cytotoxicity and elucidate its underlying mechanisms.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Inductively coupled plasma\u2012mass spectrometry was used to measure Cd concentrations in each tissue of ICR male mice. The human proximal tubule epithelial cell line HK-2 and the human retinal pigment epithelial cell line ARPE-19 were used in the <jats:italic>in vitro<\/jats:italic> study. Cell apoptosis was determined by DAPI staining, JC-1 staining, and annexin V\/propidium iodide double staining. Intracellular oxidative stress was detected by MitoSOX red staining, western blot, and quantitative real-time PCR. Moreover, ER stress signaling, MAPK cascades, and autophagy signaling were analyzed by western blot.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The present data showed that Cd accumulated in various organs of ICR mice, and the concentrations of Cd in the studied organs, from high to low, were as follows: liver &gt; kidney &gt; testis &gt; lung &gt; spleen &gt; eye. Our study demonstrated that azoramide inhibited ER stress by promoting BiP expression and suppressing the PERK-eIF2\u03b1-CHOP pathway. Additionally, we also found that azoramide significantly decreased ER stress-associated radical oxidative species production, attenuated p38 MAPK and JNK signaling, and inhibited autophagy, thus suppressing apoptosis in HK-2 and ARPE-19 cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our study investigated the effect of azoramide on Cd-induced cytotoxicity and revealed that azoramide may be a therapeutic drug for Cd poisoning.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.16844","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T08:39:16Z","timestamp":1706690356000},"page":"e16844","source":"Crossref","is-referenced-by-count":4,"title":["Azoramide ameliorates cadmium-induced cytotoxicity by inhibiting endoplasmic reticulum stress and suppressing oxidative stress"],"prefix":"10.7717","volume":"12","author":[{"given":"Lingmin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital, Wenzhou Medical University, Taizhou, Zhejiang Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital, Wenzhou Medical University, Taizhou, Zhejiang Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital, Wenzhou Medical University, Taizhou, Zhejiang Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Huangyan Hospital, Wenzhou Medical University, Taizhou, Zhejiang Province, People\u2019s Republic of 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