{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T02:21:04Z","timestamp":1775874064077,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic kidney disease of unknown etiology (CKDu), manifested clinically as tubulo interstitial fibrosis, has emerged as the second major cause of chronic kidney disease (CKD) in the Indian subcontinent and various agrochemicals have been implicated in its occurance. Among the agrochemicals organochlorine pesticides particularly endosulfan is well known for its toxicity and recent residue analysis have shown its presence in the blood samples of general population. In this present study, we have investigated the consequences of endosulfan exposure at a concentration (0.01\u2009\u03bcM) equivalent to their highest reported presence in human blood sample of some CKDu patients, to human renal proximal tubular epithelial (HK\u20102) cell line with regard to ROS generation and expression of profibrotic and epithelial to mesenchymal (EMT) markers in order to find out endosulfan's ability to induce profibrotic changes in renal cell. We demonstrated a significant increase in intracellular ROS generation and increased expression of TGF\u2010\u03b21 when cells were incubated with \u03b2\u2010endosulfan (0.01\u2009\u03bcM) indicating occurrence of oxidative stress and fibrotic process. Again, decreased expression of epithelial marker E\u2010cadherin and increase in the expression of mesenchymal marker \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) suggest possible onset of EMT process. Pre\u2010treatment with 5\u2009mM concentration of anti\u2010oxidant N\u2010acetyl cysteine partially attenuated the above process. In conclusion, these findings suggest possible involvement of \u03b2\u2010endosulfan in the development of CKDu through oxidative stress and profibrotic signaling.<\/jats:p>","DOI":"10.1002\/tox.23349","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T11:25:58Z","timestamp":1629199558000},"page":"2354-2360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["\u03b2\u2010Endosulfan\u2010mediated induction of pro\u2010fibrotic markers in renal (<scp>HK<\/scp>\u20102) cells <i>in vitro<\/i>: A new insight in the pathogenesis of chronic kidney disease of unknown etiology"],"prefix":"10.1002","volume":"36","author":[{"given":"Rishila","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Environmental Biochemistry and Immunology Laboratory University College of Medical Sciences (University of Delhi) and G.T.B. Hospital  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manushi","family":"Siddarth","sequence":"additional","affiliation":[{"name":"Multidisciplinary Research Unit University College of Medical Sciences (University of Delhi) and G.T.B. Hospital  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawan Kumar","family":"Kare","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Environmental Biochemistry and Immunology Laboratory University College of Medical Sciences (University of Delhi) and G.T.B. Hospital  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basu Dev","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Environmental Biochemistry and Immunology Laboratory University College of Medical Sciences (University of Delhi) and G.T.B. Hospital  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Om Prakash","family":"Kalra","sequence":"additional","affiliation":[{"name":"Department of Medicine University College of Medical Sciences (University of Delhi) and G.T.B. Hospital  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-966X","authenticated-orcid":false,"given":"Ashok Kumar","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Environmental Biochemistry and Immunology Laboratory University College of Medical Sciences (University of Delhi) and G.T.B. Hospital  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4038\/jccpsl.v17i1.4931"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","unstructured":"ElledgeM RedmonJH LevineK WickremasingheRJ WanigasariyaKP Peiris\u2010JohnRJ.Chronic kidney disease of unknown etiology in Sri Lanka: quest for understanding and global implications.RTI Press.2014;1\u20104.","DOI":"10.3768\/rtipress.2014.rb.0007.1405"},{"issue":"10","key":"e_1_2_9_4_1","first-page":"1","article-title":"What do we know about chronic kidney disease in India: first report of the Indian CKD registry?","volume":"13","author":"Rajapurkar MM","year":"2012","journal-title":"BMC Nephrol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.14202\/vetworld.2015.66-71"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4236\/ajac.2012.38077"},{"key":"e_1_2_9_7_1","first-page":"8","article-title":"Pesticides usage in agriculture among rural women in Egypt: association between serum organochlorine pesticide residues and occurrence of diabetes","volume":"1","author":"Sharaf NE","year":"2013","journal-title":"World J Med Sci"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21416"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12199-017-0660-5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22066"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22029"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971-6580.111575"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.37757\/MR2014.V16.N2.8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12199-011-0243-9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004050425"},{"issue":"7","key":"e_1_2_9_16_1","first-page":"688","article-title":"New insights into epithelial\u2010mesenchymal transition in kidney fibrosis","volume":"61","author":"Liu Y","year":"2010","journal-title":"Chem Pharm Bull"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c13-00066"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327119828136"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-015-0076-3"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins6061742"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.448"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8379327"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7047238"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034026"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-3371(90)90059-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.11.005"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.08.009"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2019.1577464"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.23349","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/tox.23349","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.23349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T23:08:27Z","timestamp":1693350507000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.23349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,17]]},"references-count":28,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/tox.23349"],"URL":"https:\/\/doi.org\/10.1002\/tox.23349","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,17]]},"assertion":[{"value":"2020-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}