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β‐Endosulfan‐mediated induction of pro‐fibrotic markers in renal (HK‐2) cells in vitro: A new insight in the pathogenesis of chronic kidney disease of unknown etiology
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 organoch...
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Published in: | Environmental toxicology 2021-11, Vol.36 (11), p.2354-2360 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 μM) equivalent to their highest reported presence in human blood sample of some CKDu patients, to human renal proximal tubular epithelial (HK‐2) 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‐β1 when cells were incubated with β‐endosulfan (0.01 μM) indicating occurrence of oxidative stress and fibrotic process. Again, decreased expression of epithelial marker E‐cadherin and increase in the expression of mesenchymal marker α‐smooth muscle actin (α‐SMA) suggest possible onset of EMT process. Pre‐treatment with 5 mM concentration of anti‐oxidant N‐acetyl cysteine partially attenuated the above process. In conclusion, these findings suggest possible involvement of β‐endosulfan in the development of CKDu through oxidative stress and profibrotic signaling. |
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ISSN: | 1520-4081 1522-7278 |
DOI: | 10.1002/tox.23349 |