Prenatal Exposure to Phthalic Acid Induces Increased Blood Pressure, Oxidative Stress, and Markers of Endothelial Dysfunction in Rat Offspring

Abstract

Previous studies have reported the harmful effects of exposure to phthalic acid (PA) on heart. No studies have reported the effects of prenatal PA exposure on the structure or function of heart. The current study aimed to investigate the effects of prenatal PA exposure on the markers of oxidative stress and cardiac structure in rats' offspring. Twenty-four pregnant rats were randomly categorized into three groups of control, exposed to 2.5 and 5 % PA. The morphometric properties of coronary arteries, markers of oxidative stress, and NOS activity were measured in offspring rats. By a dose-dependent manner, the body weight (BW), heart weight (HW), and HW/BW of the intervention groups were reduced and their heart rate and blood pressure were conversely increased compared to the control group. Also, the wall thickness, cross-sectional area of the aorta and septal branch of the descending left coronary artery were significantly increased in the intervention group. In addition, PA significantly increased the level of malondialdehyde and decreased the level of superoxide dismutase and glutathione peroxidase, compared to the control group. This study revealed that prenatal exposure of rats to PA causes vascular dysfunction, increasing oxidative stress, and reduction in cardiac nitric oxide synthetase activity among offspring rats.

Phthalates Implications in the Cardiovascular System

“…The mice systolic BP measurements showed a significant increase (22%) after 10 mg/kg/day DEHP exposure, which was consistent with the findings of Lee et al where a 30 mg/kg/day maternal DEHP exposure increased the systolic BP by 20% [ 29 , 32 ]. These results were also proved by the authors through the histopathological analysis, which showed a significant thickening of the interventricular septum and the ventricular wall at the same dosage, which were in accordance with the histopathological results of the Rahmani et al study [ 30 ]. Then, the authors measured the levels of ACE, bradykinin B2 receptor (BK2R), eNOS, bradykinin, Ca 2+ , and NO, all related with blood pressure regulation.…”

“…The authors showed a significant increase in the offspring BP associated with the increased phthalic acid exposure due to cardiac hypertrophy and a significant increase in the thickness of the aorta wall and the descending left coronary artery. It was also demonstrated that phthalic acid significantly increased the oxidative stress and decreased the antioxidant capacity of the cardiac tissue, which, in turn, are related to vascular dysfunction [ 30 ]. In 2017, Jaimes et al showed that mice exposed to DEHP suffered alterations in the heart rate and cardiovascular response.…”

“…All of these studies show that DEHP exposure has the ability to elevate BP [ 29 , 30 , 31 , 32 , 34 ], as well as another HMW phthalate, the DiNP [ 33 ]. However, the only LMW phthalate studied did not lead to a significant change in blood pressure [ 34 ].…”

Sex-Specific Programming of Cardiac DNA Methylation by Developmental Phthalate Exposure

“… 19 , 20 Importantly, the majority of studies investigating the effects of gestational phthalate exposures on cardiovascular outcomes have focused only on males. 11 , 12 , 21 Although work from our lab and others demonstrate sexually dimorphic effects of endocrine-disrupting chemicals, including phthalates, in humans and animal models, 6 , 22 - 24 little is known about the sex-specific effects of gestational exposure to phthalates on the heart.…”

“… 6 - 9 Recent animal studies have also linked gestational phthalate exposures to altered heart development and function. 10 - 12 Likewise, human studies demonstrate an association between both pediatric and adult phthalate exposure and adverse cardiovascular outcomes. 13 - 16 However, few studies in humans have investigated the effects of perinatal exposures on cardiovascular health.…”