Diglycolic acid induces HepG2/C3A liver cell toxicity in vitro

Mossoba, Miriam E.; Vohra, Sanah; Toomer, Howard; Pugh-Bishop, Shelia; Keltner, Zachary; Topping, Vanessa; Black, T.N.; Olejnik, Nicholas; DePina, Ana S.; Belgrave, Kathleen; Sprando, Jessica; Flynn, Tom; Wiesenfeld, Paddy L.; Sprando, Robert L.

doi:10.1016/j.tiv.2018.06.006

Cited by 6 publications

(3 citation statements)

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“…The identification and characterization of DGA as a renal and hepatic toxicant has been unequivocally established using in vitro cellular, in vivo rat, and even human systems [3,[7][8][9][10]. A single case report of human exposure indicated that the heart could be negatively affected by DGA, but this effect has never been previously captured in vitro or in vivo animal models.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were exposed to concentrations of DGA from 0.5 to 10 mM for a 24 hour period, similar to our other studies [7,8,16,17]. Cytotoxicity was assessed using a kit for ATP content (Promega, Madison, WI, USA) according to the manufacturer's instructions, except for prior rinsing of wells to avoid interference of the test compounds with light production [16].…”

Section: Cytotoxicity and Reactive Oxygen Species Evaluation In H9c2 mentioning

confidence: 99%

“…In the absence of published in vivo dose-response and lethal dose (LD)50 data on DGA, we sought out to begin investigating the potential for DGA to engender toxicity. Human in vitro and rat in vivo studies by our group and others have established that DGA is an acute renal and hepatic toxin, with the potential of also being a cardiotoxin [5][6][7][8][9][10]. In a tragic case report of unintentional human DGA oral exposure, not only were the kidneys and liver severely damaged, but there was some evidence of heart injury as well [9].…”

Section: Introductionmentioning

confidence: 99%

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Cardiotoxicity testing of diglycolic acid using In Vitro and In Vivo models

Calvert¹,

Mossoba²,

Bailey³

et al. 2017

J Toxicol Health

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Background: Renal and hepatotoxicity of diglycolic acid (DGA) has been described with in vitro cellular models as well as in vivo animal and human systems. The possibility of DGA being toxic to other organs, such as the heart, has not been well investigated. A human case report identified the heart as a potential target organ of DGA, but an in-house in vivo rat study neither found gross nor microscopic pathological changes following repeated oral DGA exposure. Methods: To better understand the potential of DGA to adversely affect the heart, we focused our current study on evaluating cardiac effects of DGA by treating rat H9c2 cardiomyocytes and human induced pluripotent stem cells (iPSCs) that were differentiated into beating cardiomyocytes (iCells) with increasing concentrations of DGA in cell culture media. We investigated the effects, mechanisms, and value of our in vitro cellular cardiac models. Results: We measured mild effects of DGA on cytotoxicity and the cellular production of reactive oxygen species in H9c2 cells. Cardiomyocyte beat rate (BPM) was also mildly affected by transient treatment with DGA. Conclusions: Our study indicates that DGA cardiotoxicity in vitro correlates with the preliminary findings in our in vivo study where rats treated with daily doses of up to 300 mg/kg of DGA orally for 5 days did not show any major signs of abnormal cardiac pathology.

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