Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage
Chromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However,...
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MDPI AG
2019-08-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/9/9/172 |
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| author | I-Jeng Yeh Tzu-Yi Wang Jhong-Ching Lin Tzeng-Jih Lin Jung-San Chang Meng-Chi Yen Yao-Hua Liu Pei-Lin Wu Fen-Wei Chen Yueh-Lun Shih Chiung-Yu Peng |
| author_facet | I-Jeng Yeh Tzu-Yi Wang Jhong-Ching Lin Tzeng-Jih Lin Jung-San Chang Meng-Chi Yen Yao-Hua Liu Pei-Lin Wu Fen-Wei Chen Yueh-Lun Shih Chiung-Yu Peng |
| author_sort | I-Jeng Yeh |
| collection | DOAJ |
| description | Chromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However, the optimal regimen and protective mechanisms of NAC are not fully understood in human renal cells. Our results showed that exposure to 10 μM K<sub>2</sub>Cr<sub>2</sub>O<sub>7</sub>, a toxic Cr(VI) compound, induced apoptosis and production of intracellular ROS in the human proximal tubular epithelial cell line HK-2. Supplements of 600 or 1000 µg/mL NAC inhibited intracellular ROS in HK-2 cells exposed to Cr(VI) and significantly increased cell viability within 2 h of Cr(VI)-induced cytotoxicity. Moreover, Cr(VI) induced the expression of apoptosis markers, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, cleaved-caspase 8, and cleaved-caspase 9, and altered the expression ratio of Bax/Bcl-xL. Expression of apoptosis markers within 2 h of Cr(VI)-induced cytotoxicity in cells treated with 600 µg/mL NAC was significantly suppressed. However, delayed treatment with NAC at 4 h and 8 h after exposure to Cr did not suppress the activation of apoptotic pathways. In summary, our study reports the optimum timing and dose of NAC for the protection of human renal proximal tubular cells from Cr(VI)-induced cell death. The NAC treatment strategy described could be applied in clinical practice to suppress renal cell apoptosis, which in turn could rescue renal function. |
| first_indexed | 2024-12-10T20:59:55Z |
| format | Article |
| id | doaj.art-7a76dfd231a946d09e1cd1c35645a800 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-12-10T20:59:55Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-7a76dfd231a946d09e1cd1c35645a8002022-12-22T01:33:51ZengMDPI AGMetabolites2218-19892019-08-019917210.3390/metabo9090172metabo9090172Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell DamageI-Jeng Yeh0Tzu-Yi Wang1Jhong-Ching Lin2Tzeng-Jih Lin3Jung-San Chang4Meng-Chi Yen5Yao-Hua Liu6Pei-Lin Wu7Fen-Wei Chen8Yueh-Lun Shih9Chiung-Yu Peng10Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanFamily Medicine Department, Taoyuan Branch, Taipei Veterans General Hospital, Taipei 112, TaiwanDepartment of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung 807, TaiwanChromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However, the optimal regimen and protective mechanisms of NAC are not fully understood in human renal cells. Our results showed that exposure to 10 μM K<sub>2</sub>Cr<sub>2</sub>O<sub>7</sub>, a toxic Cr(VI) compound, induced apoptosis and production of intracellular ROS in the human proximal tubular epithelial cell line HK-2. Supplements of 600 or 1000 µg/mL NAC inhibited intracellular ROS in HK-2 cells exposed to Cr(VI) and significantly increased cell viability within 2 h of Cr(VI)-induced cytotoxicity. Moreover, Cr(VI) induced the expression of apoptosis markers, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, cleaved-caspase 8, and cleaved-caspase 9, and altered the expression ratio of Bax/Bcl-xL. Expression of apoptosis markers within 2 h of Cr(VI)-induced cytotoxicity in cells treated with 600 µg/mL NAC was significantly suppressed. However, delayed treatment with NAC at 4 h and 8 h after exposure to Cr did not suppress the activation of apoptotic pathways. In summary, our study reports the optimum timing and dose of NAC for the protection of human renal proximal tubular cells from Cr(VI)-induced cell death. The NAC treatment strategy described could be applied in clinical practice to suppress renal cell apoptosis, which in turn could rescue renal function.https://www.mdpi.com/2218-1989/9/9/172apoptosishexavalent chromiumhuman proximal tubular epithelial cellN-acetylcysteine (NAC), reactive oxygen species |
| spellingShingle | I-Jeng Yeh Tzu-Yi Wang Jhong-Ching Lin Tzeng-Jih Lin Jung-San Chang Meng-Chi Yen Yao-Hua Liu Pei-Lin Wu Fen-Wei Chen Yueh-Lun Shih Chiung-Yu Peng Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage Metabolites apoptosis hexavalent chromium human proximal tubular epithelial cell N-acetylcysteine (NAC), reactive oxygen species |
| title | Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage |
| title_full | Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage |
| title_fullStr | Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage |
| title_full_unstemmed | Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage |
| title_short | Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage |
| title_sort | optimal regimen of n acetylcysteine on chromium induced renal cell damage |
| topic | apoptosis hexavalent chromium human proximal tubular epithelial cell N-acetylcysteine (NAC), reactive oxygen species |
| url | https://www.mdpi.com/2218-1989/9/9/172 |
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