Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells
Globally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxida...
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Wiley
2021-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2021/6634429 |
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| author | Chandrashekar Annamalai Rohit Seth Pragasam Viswanathan |
| author_facet | Chandrashekar Annamalai Rohit Seth Pragasam Viswanathan |
| author_sort | Chandrashekar Annamalai |
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| description | Globally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxidation. In addition, 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, is reported to have an antioxidative role. In this study, we intended to demonstrate the impact of vitamin D on iron-mediated oxidant stress and cytotoxicity of Vero cells exposed to iohexol, a low osmolar iodine-containing contrast media in vitro. Cultured Vero cells were pretreated with 1,25-dihydroxyvitamin D3 dissolved in absolute ethanol (0.05%, 2.0 mM) at a dose of 1 mM for 6 hours. Subsequently, iohexol was added at a concentration of 100 mg iodine per mL and incubated for 3 hours. Total cellular iron content was analysed by a flame atomic absorption spectrophotometer at 372 nm. Lipid peroxidation was determined by TBARS (thiobarbituric acid reactive species) assay. Antioxidants including total thiol content were assessed by Ellman’s method, catalase by colorimetric method, and superoxide dismutase (SOD) by nitroblue tetrazolium assay. The cells were stained with DAPI (4′,6-diamidino-2-phenylindole), and the cytotoxicity was evaluated by viability assay (MTT assay). The results indicated that iohexol exposure caused a significant increase of the total iron content in Vero cells. A concomitant increase of lipid peroxidation and decrease of total thiol protein levels, catalase, and superoxide dismutase activity were observed along with decreased cell viability in comparison with the controls. Furthermore, these changes were significantly reversed when the cells were pretreated with vitamin D prior to incubation with iohexol. Our findings of this in vitro model of iohexol-induced renotoxicity lend further support to the nephrotoxic potential of iron and underpin the possible clinical utility of vitamin D for the treatment and prevention of AKI. |
| format | Article |
| id | doaj-art-5d0986907a784a26886f9f99a15f7c1b |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Analytical Cellular Pathology |
| spelling | doaj-art-5d0986907a784a26886f9f99a15f7c1b2025-08-20T03:34:14ZengWileyAnalytical Cellular Pathology2210-71772210-71852021-01-01202110.1155/2021/66344296634429Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal CellsChandrashekar Annamalai0Rohit Seth1Pragasam Viswanathan2Renal Research Lab, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632 014 Tamil Nadu, IndiaDepartment of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, 495009 Chhattisgarh, IndiaRenal Research Lab, Centre for Biomedical Research, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632 014 Tamil Nadu, IndiaGlobally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxidation. In addition, 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, is reported to have an antioxidative role. In this study, we intended to demonstrate the impact of vitamin D on iron-mediated oxidant stress and cytotoxicity of Vero cells exposed to iohexol, a low osmolar iodine-containing contrast media in vitro. Cultured Vero cells were pretreated with 1,25-dihydroxyvitamin D3 dissolved in absolute ethanol (0.05%, 2.0 mM) at a dose of 1 mM for 6 hours. Subsequently, iohexol was added at a concentration of 100 mg iodine per mL and incubated for 3 hours. Total cellular iron content was analysed by a flame atomic absorption spectrophotometer at 372 nm. Lipid peroxidation was determined by TBARS (thiobarbituric acid reactive species) assay. Antioxidants including total thiol content were assessed by Ellman’s method, catalase by colorimetric method, and superoxide dismutase (SOD) by nitroblue tetrazolium assay. The cells were stained with DAPI (4′,6-diamidino-2-phenylindole), and the cytotoxicity was evaluated by viability assay (MTT assay). The results indicated that iohexol exposure caused a significant increase of the total iron content in Vero cells. A concomitant increase of lipid peroxidation and decrease of total thiol protein levels, catalase, and superoxide dismutase activity were observed along with decreased cell viability in comparison with the controls. Furthermore, these changes were significantly reversed when the cells were pretreated with vitamin D prior to incubation with iohexol. Our findings of this in vitro model of iohexol-induced renotoxicity lend further support to the nephrotoxic potential of iron and underpin the possible clinical utility of vitamin D for the treatment and prevention of AKI.http://dx.doi.org/10.1155/2021/6634429 |
| spellingShingle | Chandrashekar Annamalai Rohit Seth Pragasam Viswanathan Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells Analytical Cellular Pathology |
| title | Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells |
| title_full | Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells |
| title_fullStr | Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells |
| title_full_unstemmed | Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells |
| title_short | Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells |
| title_sort | ferrotoxicity and its amelioration by calcitriol in cultured renal cells |
| url | http://dx.doi.org/10.1155/2021/6634429 |
| work_keys_str_mv | AT chandrashekarannamalai ferrotoxicityanditsameliorationbycalcitriolinculturedrenalcells AT rohitseth ferrotoxicityanditsameliorationbycalcitriolinculturedrenalcells AT pragasamviswanathan ferrotoxicityanditsameliorationbycalcitriolinculturedrenalcells |