{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:40:38Z","timestamp":1775256038314,"version":"3.50.1"},"reference-count":48,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"HHS | NIH | NIH Office of the Director & NIAMS","award":["R21AR064595"],"award-info":[{"award-number":["R21AR064595"]}]},{"name":"HHS | NIH | NIH Office of the Director & NIAMS","award":["UO1NS095678"],"award-info":[{"award-number":["UO1NS095678"]}]},{"name":"NIH","award":["R01 DK59600"],"award-info":[{"award-number":["R01 DK59600"]}]},{"name":"NIH","award":["P30 DK079337"],"award-info":[{"award-number":["P30 DK079337"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:p> Lewisite (2-chlorovinyldichloroarsine) is an organic arsenical chemical warfare agent that was developed and weaponized during World Wars I\/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only the result of cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analog phenylarsine oxide (PAO) in a murine model. Both agents caused renal tubular injury, characterized by loss of brush border in proximal tubules and tubular cell apoptosis accompanied by increases in serum creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Interestingly, lewisite exposure enhanced production of reactive oxygen species (ROS) in the kidney and resulted in the activation of autophagic and DNA damage response (DDR) signaling pathways with increased expression of beclin-1, autophagy-related gene 7, and LC-3A\/B-II and increased phosphorylation of \u03b3-H<jats:sub>2<\/jats:sub>A.X and checkpoint kinase 1\/2, respectively. Terminal deoxyribonucleotide-transferase-mediated dUTP nick-end labeling-positive cells were detected in renal tubules along with enhanced proapoptotic BAX\/cleaved caspase-3 and reduced antiapoptotic BCL<jats:sub>2<\/jats:sub>. Scavenging ROS by cutaneous postexposure application of the antioxidant N-acetyl-l-cysteine reduced lewisite-induced autophagy and DNA damage. In summary, we provide evidence that topical exposure to lewisite causes AKI. The molecular mechanism underlying these changes involves ROS-dependent activation of autophagy and DDR pathway associated with the induction of apoptosis. <\/jats:p>","DOI":"10.1152\/ajprenal.00277.2017","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T13:58:27Z","timestamp":1516197507000},"page":"F1166-F1176","source":"Crossref","is-referenced-by-count":31,"title":["Cutaneous exposure to lewisite causes acute kidney injury by invoking DNA damage and autophagic response"],"prefix":"10.1152","volume":"314","author":[{"given":"Ritesh K.","family":"Srivastava","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amie M.","family":"Traylor","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Birmingham Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changzhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenguang","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Birmingham Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Birmingham Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veena B.","family":"Antony","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trenton R.","family":"Schoeb","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anupam","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Birmingham Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Athar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00049.2017"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00335.2015"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010030238"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.761_2.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.99107663"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4450.607"},{"key":"B8","unstructured":"Davis MI. 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