Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate

TY - JOUR

T1 - Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate

AU - Sachdeva, Sherry

AU - Maret, Wolfgang

N1 - Funding Information: The authors thank Andy Cakebread for metal analyses, Dr. Elisa Bellomo and Dr. Douglas Parsons for training Sherry Sachdeva with cell culture, Dr. Kshetrimayum Birla Singh, Dr. Sandra Carvalho and Prof. Christer Hogstrand for discussions. S.S. thanks the Director, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India and Dr. S.J.S. Flora for their support and encouragement. S.S. thanks the Department of Science and Technology, India and British Council UK for providing the financial support through a Newton-Bhabha fellowship. . Funding Information: Department of Science and Technology, India and British Council UK (Newton-Bhabha Fund) (DST/INSPIRE/NBHF/2014/22). The authors thank Andy Cakebread for metal analyses, Dr. Elisa Bellomo and Dr. Douglas Parsons for training Sherry Sachdeva with cell culture, Dr. Kshetrimayum Birla Singh, Dr. Sandra Carvalho and Prof. Christer Hogstrand for discussions. S.S. thanks the Director, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India and Dr. S.J.S. Flora for their support and encouragement. S.S. thanks the Department of Science and Technology, India and British Council UK for providing the financial support through a Newton-Bhabha fellowship. Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021

Y1 - 2021

N2 - Tungsten has no known function in humans and is a relatively new contaminant, whereas molybdenum, its congener in the periodic table, is a nutritionally essential element. In addition to early studies on molybdosis in ruminants, their toxic effects in the form of tungstate and molybdate have been addressed primarily in rodents and are predominantly mediated by inducing oxidative stress in various tissues. The purpose of this study was to evaluate the differences between tungstate and molybdate in human liver (HepG2) and kidney (HEK293) cell lines in terms of retention in cells, effect on reactive oxygen species, and activities of xanthine oxidase and phosphatases. The cell lines were exposed to tungstate or molybdate (1 µM to 10 mM) for 24 h, lysed and analyzed for the above biochemical parameters. Despite the chemical similarity of the two anions, cell-specific differential effects were observed. At all concentrations, tungstate was retained more in HEK293 cells while molybdate was retained more in HepG2 cells. HepG2 cells were more sensitive to tungstate than molybdate, showing reduced viability at concentrations as low as 10 µM. Exposure to either anion resulted in the inhibition of protein tyrosine phosphatases at 1 mM and an increased production of reactive oxygen species (ROS) at 100 µM despite their inhibition of the ROS-producing molybdenum enzyme xanthine oxidase. In conclusion, the results indicate that excess of nutritionally essential molybdate or non-essential tungstate causes toxicity by affecting ROS- and phosphorylation-dependent signaling pathways and ensuing gene expression.

AB - Tungsten has no known function in humans and is a relatively new contaminant, whereas molybdenum, its congener in the periodic table, is a nutritionally essential element. In addition to early studies on molybdosis in ruminants, their toxic effects in the form of tungstate and molybdate have been addressed primarily in rodents and are predominantly mediated by inducing oxidative stress in various tissues. The purpose of this study was to evaluate the differences between tungstate and molybdate in human liver (HepG2) and kidney (HEK293) cell lines in terms of retention in cells, effect on reactive oxygen species, and activities of xanthine oxidase and phosphatases. The cell lines were exposed to tungstate or molybdate (1 µM to 10 mM) for 24 h, lysed and analyzed for the above biochemical parameters. Despite the chemical similarity of the two anions, cell-specific differential effects were observed. At all concentrations, tungstate was retained more in HEK293 cells while molybdate was retained more in HepG2 cells. HepG2 cells were more sensitive to tungstate than molybdate, showing reduced viability at concentrations as low as 10 µM. Exposure to either anion resulted in the inhibition of protein tyrosine phosphatases at 1 mM and an increased production of reactive oxygen species (ROS) at 100 µM despite their inhibition of the ROS-producing molybdenum enzyme xanthine oxidase. In conclusion, the results indicate that excess of nutritionally essential molybdate or non-essential tungstate causes toxicity by affecting ROS- and phosphorylation-dependent signaling pathways and ensuing gene expression.

KW - HEK293 cells

KW - HepG2 cells

KW - molybdenum

KW - toxicity outcomes

KW - Tungsten

UR - http://www.scopus.com/inward/record.url?scp=85111837365&partnerID=8YFLogxK

U2 - 10.1080/15376516.2021.1956031

DO - 10.1080/15376516.2021.1956031

M3 - Article

AN - SCOPUS:85111837365

SN - 1537-6524

VL - 31

SP - 690

EP - 698

JO - TOXICOLOGY MECHANISMS AND METHODS

JF - TOXICOLOGY MECHANISMS AND METHODS

IS - 9

ER -