Hexavalent chromium intoxication induces intrinsic and extrinsic apoptosis in human renal cells

Wu,Yen‑Hung; Lin,Jhong‑Ching; Wang,Tzu‑Yi; Lin,Tzeng‑Jih; Yen,Meng‑Chi; Liu,Yao‑Hua; Wu,Pei‑Lin; Chen,Fen‑Wei; Shih,Yueh‑Lun; Yeh,I‑Jeng

doi:10.3892/mmr.2019.10885

Hexavalent chromium intoxication induces intrinsic and extrinsic apoptosis in human renal cells

Authors:
- Yen‑Hung Wu
- Jhong‑Ching Lin
- Tzu‑Yi Wang
- Tzeng‑Jih Lin
- Meng‑Chi Yen
- Yao‑Hua Liu
- Pei‑Lin Wu
- Fen‑Wei Chen
- Yueh‑Lun Shih
- I‑Jeng Yeh
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Affiliations: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Department of Family Medicine, Taoyuan Branch, Taipei Veterans General Hospital, Taoyuan 330, Taiwan, R.O.C.
Published online on: December 16, 2019 https://doi.org/10.3892/mmr.2019.10885
Pages: 851-857
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hexavalent chromium [Cr(VI)], is a well‑known toxic form of the heavy metal chromium in the natural environment. Clinical evidence has indicated that exposure to Cr(VI) can cause severe renal damage. The production of reactive oxygen species (ROS) due to intracellular reduction of Cr(VI) is the main mechanism underlying the induction of cellular dysfunction and apoptosis. The present study aimed to investigate in detail the apoptotic pathways induced by Cr(VI)‑exposure in a human immortalized proximal tubular epithelial cell line HK‑2, in order to understand the mechanism involved therein. Exposure to 10 µM potassium dichromate (K2Cr2O7), a toxic compound of Cr(VI), significantly decreased cell viability after 24 and 48 h of incubation and induced intracellular ROS generation. The expression levels of markers that activate the apoptotic pathway including cleaved caspase‑3 and poly (ADP‑ribose) polymerase were significantly upregulated in K2Cr2O7‑exposed HK‑2 cells. In addition, the induction of intrinsic and extrinsic apoptotic markers was detected in K2Cr2O7‑exposed HK‑2 cells. In summary, the present study described for the first time the novel apoptotic mechanism of Cr(VI)‑toxicity in human renal cells which may be beneficial in designing optimal clinical treatment for renal damage caused by acute Cr(VI) toxicity.

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