Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo
Diglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening in...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-01-01
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| Series: | Toxicology Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750017300422 |
| _version_ | 1818855568565075968 |
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| author | Miriam E. Mossoba Sanah Vohra Howard Toomer Shelia Pugh-Bishop Zachary Keltner Vanessa Topping Thomas Black Nicholas Olejnik Ana Depina Kathleen Belgrave Jessica Sprando Joyce Njorge Thomas J. Flynn Paddy L. Wiesenfeld Robert L. Sprando |
| author_facet | Miriam E. Mossoba Sanah Vohra Howard Toomer Shelia Pugh-Bishop Zachary Keltner Vanessa Topping Thomas Black Nicholas Olejnik Ana Depina Kathleen Belgrave Jessica Sprando Joyce Njorge Thomas J. Flynn Paddy L. Wiesenfeld Robert L. Sprando |
| author_sort | Miriam E. Mossoba |
| collection | DOAJ |
| description | Diglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening ingredient in many other processed foods. We sought to utilize the human proximal tubule HK-2 cell line as an in vitro cellular model system to evaluate its acute nephrotoxicity of DGA. We found that DGA was indeed toxic to HK-2 cells in all in vitro assays in our study, including a highly sensitive Luminex assay that measures levels of an in vitro biomarker of kidney-specific toxicity, Kidney Injury Molecule 1 (KIM-1). Interestingly, in vitro KIM-1 levels also correlated with in vivo KIM-1 levels in urine collected from rats treated with DGA by daily oral gavage. The use of in vitro and in vivo models towards understanding the effectiveness of an established in vitro system to predict in vivo outcomes would be particularly useful in rapidly screening compounds that are suspected to be unsafe to consumers. The merit of the HK-2 cell model in predicting human toxicity and accelerating the process of food toxicant screening would be especially important for regulatory purposes. Overall, our study not only revealed the value of HK-2 in vitro cell model for nephrotoxicity evaluation, but also uncovered some of the mechanistic aspects of the human proximal tubule injury that DGA may cause. Keywords: Kidney proximal tubule, HK-2 cells, Diglycolic acid, Nephrotoxicity |
| first_indexed | 2024-12-19T08:10:40Z |
| format | Article |
| id | doaj.art-33362497970a424f9240161a3482ee43 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-19T08:10:40Z |
| publishDate | 2017-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-33362497970a424f9240161a3482ee432022-12-21T20:29:39ZengElsevierToxicology Reports2214-75002017-01-014342347Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivoMiriam E. Mossoba0Sanah Vohra1Howard Toomer2Shelia Pugh-Bishop3Zachary Keltner4Vanessa Topping5Thomas Black6Nicholas Olejnik7Ana Depina8Kathleen Belgrave9Jessica Sprando10Joyce Njorge11Thomas J. Flynn12Paddy L. Wiesenfeld13Robert L. Sprando14Corresponding author at: US FDA, MOD-1 Laboratories, 8301 Muirkirk Rd., HFS-025, Lab 1406, Laurel, MD 20708, United States.; U.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesU.S. Food and Drug Administration (US FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Applied Research and Safety Assessment (OARSA), Division of Toxicology (DOT), 8301 Muirkirk Rd., Laurel, MD 20708, United StatesDiglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening ingredient in many other processed foods. We sought to utilize the human proximal tubule HK-2 cell line as an in vitro cellular model system to evaluate its acute nephrotoxicity of DGA. We found that DGA was indeed toxic to HK-2 cells in all in vitro assays in our study, including a highly sensitive Luminex assay that measures levels of an in vitro biomarker of kidney-specific toxicity, Kidney Injury Molecule 1 (KIM-1). Interestingly, in vitro KIM-1 levels also correlated with in vivo KIM-1 levels in urine collected from rats treated with DGA by daily oral gavage. The use of in vitro and in vivo models towards understanding the effectiveness of an established in vitro system to predict in vivo outcomes would be particularly useful in rapidly screening compounds that are suspected to be unsafe to consumers. The merit of the HK-2 cell model in predicting human toxicity and accelerating the process of food toxicant screening would be especially important for regulatory purposes. Overall, our study not only revealed the value of HK-2 in vitro cell model for nephrotoxicity evaluation, but also uncovered some of the mechanistic aspects of the human proximal tubule injury that DGA may cause. Keywords: Kidney proximal tubule, HK-2 cells, Diglycolic acid, Nephrotoxicityhttp://www.sciencedirect.com/science/article/pii/S2214750017300422 |
| spellingShingle | Miriam E. Mossoba Sanah Vohra Howard Toomer Shelia Pugh-Bishop Zachary Keltner Vanessa Topping Thomas Black Nicholas Olejnik Ana Depina Kathleen Belgrave Jessica Sprando Joyce Njorge Thomas J. Flynn Paddy L. Wiesenfeld Robert L. Sprando Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo Toxicology Reports |
| title | Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo |
| title_full | Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo |
| title_fullStr | Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo |
| title_full_unstemmed | Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo |
| title_short | Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo |
| title_sort | comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo |
| url | http://www.sciencedirect.com/science/article/pii/S2214750017300422 |
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