WITHDRAWN: Respiratory exposure to inert particulate matter during pregnancy leads to oxidative stress and cardiac proteome remodeling

Abstract

Titanium dioxide (TiO2), a particle with widespread presence in manufacturing industries, is used as a control in pollution studies. Of importance, TiO2 exposure has been shown to cause pulmonary inflammation and immune dysfunction. During pregnancy, increased cardiovascular stress occurs, inducing or aggravating conditions such as high blood pressure, diabetes, and preeclampsia. While a relation between particle exposure and cardiovascular disease has been observed, its role during pregnancy requires further understanding. Herein, we investigated the effect of TiO2 exposure on cardiac tissue in vitro and in vivo. In vitro studies using human cardiomyocytes showed TiO2 increased toxicity and necrotic death associated with enhanced oxidative stress. The use of N-acetylcysteine (NAC), a general antioxidant, rescued the myocytes from TiO2-induced necrotic death. Pregnant (P) or non-pregnant (NP) mice were challenged with TiO2 to assess the effect of pregnancy and exposure in cardiac tissue. Pregnancy alone was shown to alter the cardiac proteome with upregulation of inflammation biomarkers. Upon exposure, both P and NP mice showed notable proteome remodeling with pathways associated with oxidative stress, cardiac function, cell death, and inflammation being altered. Immunoblots confirmed changes in catalase, Complement (C) 5, and glutathione S-transferase mu 1 (GSTM1). These findings demonstrate that TiO2 can cause cardiac damage with characteristics similar to those in myocardial infarction and ischemia. Exposure during pregnancy can exacerbate some of these effects. Preventative measures should be taken to limit exposure and future studies could indicate long-term exposure impacts.