High fructose diet modulates the effects of cadmium exposure on maternal cardiac health outcomes.
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Background and purpose: Cadmium (Cd) is an environmental pollutant of increasing concern, as the number of reports indicating adverse health outcomes following environmental exposure to the heavy metal continues to grow. However, exposure to Cd does not occur in isolation, and is often confounded by various environmental stressors, including diet. Chronic overconsumption of fructose is also known to have adverse health effects, and similarly to Cd, is a cardiovascular toxicant. The purpose of this study was to investigate the ways in which overconsumption of fructose modulates the effects of Cd exposure on maternal cardiac health outcomes. Methods: Female CD-1 mice were exposed to 0.0 ppm, 0.5 ppm, or 5.0 ppm cadmium chloride (CdCl2) via drinking water ± 59% high fructose diet (HFrD) for two weeks prior to breeding and through gestation day (GD) 18. Maternal cardiac function was periodically monitored using a high-frequency echocardiography ultrasound system. Percent change data between GD8 and GD18 were calculated for each endpoint. Data were analyzed using a 2-way ANOVA with Dunnett’s post hoc test. Results and Discussion: By GD8, 3 weeks after initiation of exposures, a significant HFrD effect was detected for both stroke volume and cardiac output (control diet > HFrD; p<0.05). These effects were resolved by GD18. However, at GD18, a significant interaction of diet and CdCl2 exposure was found for ejection fraction and fractional shortening (p<0.05). Unsurprisingly, left ventricular wall thickness was increased in mice exposed to 5.0 ppm CdCl2 relative to controls (p<0.05), indicating CdCl2 may play a role in inducing left ventricular wall thickening. A significant effect of CdCl2 was also detected for left ventricular mass. These CdCl2-induced effects were undetected in mice fed HFrD. From GD8 to GD18, the percent change in heart rate (HR) was significantly increased by CdCl2 concentration for the control diet group (p<0.05). However, for the HFrD group, an inverse trend could be observed. This data demonstrates maternal exposure to CdCl2 may lead to hypertrophic cardiomyopathy, which can increase the risk of heart failure during gestation. Furthermore, this effect can be modulated by exposure to a diet high in fructose and suggests the likelihood that interactions between multiple stressors contribute to the development of adverse maternal health outcomes. (This abstract does not necessarily reflect USEPA policy.)