Effects of Long-term Nonylphenol Exposure on Myocardial Fibrosis and Cardiac Function in Rats

Abstract

Background: Myocardial fibrosis is a critical pathological basis for the poor prognosis of cardiovascular diseases. Studies have found that myocardial fibrosis is closely associated with exposure to environmental estrogens such as nonylphenol (NP), as a representative of environmental estrogens. The aim of this study was to examine the effects of NP chronic exposure on myocardial fibrosis as well as cardiac structure and function. Forty Sprague Dawley rats were randomly divided into four groups (n = 10): control group (C), low NP dose (0.4 mg/kg, L), medium NP dose (4 mg/kg, M), and high NP dose (40 mg/kg, H) groups. The NP dose groups were gavaged with NP for 180 days. Results: The NP level in the heart of the NP groups was significantly higher than those in the control group (F = 43.658, P < 0.001). Serum aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isozyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) significantly increased in the NP groups compared with the control group (). Histopathological examination of the heart biopsy illustrates that in the medium and high NP groups, the fibrous connective tissue had a disordered and loose gridding shape, muscle fibers had fractured, and muscle fibers were loose with a widened gap. Extensive inflammatory cell infiltration and fibroblast proliferation in the myocardial interstitium were also found. With increasing NP dose, the degree of muscle fiber loosing and disorder became more significant in the NP treatment groups, and the collagen volume fraction (CVF) was higher than that in the control group (P < 0.01). Compared with the control group, the expression of collagen I and collagen III increased significantly in the medium and high NP groups (P < 0.05). The values of the systolic thickness of the left ventricular anterior wall (LVAWs), the diastolic thickness of the left ventricular posterior wall (LVPWd), the systolic thickness of the left ventricular posterior wall (LVPWs), and the left ventricular anterior wall (LVAWd) in the NP groups are were slightly lower than those in of the control group. The values of left ventricular end systolic dimensions (LVIDs) in the NP groups increased compared with the control group. Conclusions: Long-term NP exposure could lead to fibrosis in the rat myocardium, which is characterized by increased expressions of myocardial collagen I and collagen III, as well as elevated cardiac enzymes. In addition, the cardiac structure was affected and changes were observed in the thinner ventricular wall and as an enlarged ventricular cavity.

Extracellular vesicles secreted by human cardiosphere-derived cells attenuate electrophysiological remodelling in an in vitro model of atrial fibrillation

“…At systemic level, D-gal is also described to decrease antioxidant and total antioxidant capacity levels [413]. However, in this study, D-gal only induced moderate changes at cardiac and systemic level: for example, no differences were observed between healthy and D-gal animals at hemodynamic and cardiac perfusion level and only moderate changes in GLB1 expression, hypertrophy and cardiac fibrosis were observed, being the values and differences still far from those of naturally aged of pathological animals [140,[414][415][416]. Therefore, as D-gal did not induce large damage at cellular, structural, and functional level, we cannot consider these animals as truly aged or pathological, giving little room for the P-EVs to exert any significant benefits.…”

“…In addition, although the results go in the direction of our hypothesis and show differences between the changes induced by EVs classified as potent and non-potent in vivo, the cardiac aging model used also presents some limitations. In particular, we only observed moderate differences between healthy and D-gal (aged) animals at molecular and structural level, and none at functional level, being the values and differences still far from those of naturally aged of pathological animals [140,[414][415][416]. This, together with the relatively low number of animals included in this study, make it difficult to see the potential small differences caused either by the model or by the potent EVs.…”

Curative effect of zinc‐selenium tea on rat's cardiotoxicity induced by long‐term exposure to nonylphenol

“…NP is mainly metabolized in the liver and kidney and accumulated in lipolytic organs. Our study showed that cardiac tissue accumulation reached 54.61 ng/mg after 180 days of exposure to 40 mg/kg NP 1 . It has also been reported that up to 80% of orally ingested NP is rapidly absorbed 2 and metabolized by the liver with high hepatic and renal clearance 3 .…”

“…NP is toxic to multiple organs and systems 33 . Our prior studies demonstrated that heart is the target organ of NP's toxicity 1 . In this study, the long‐term intragastric administration of NP to rats and the intervention of ordinary green tea and zinc‐selenium tea were the first to explore the effect of tea on the cardiotoxicity of rats caused by NP exposure, and then to compare the intervention of zinc‐selenium tea and ordinary green tea.…”

“…33 Our prior studies demonstrated that heart is the target organ of NP's toxicity. 1 In this study, the long-term intragastric administration of NP to rats and the intervention of ordinary green tea and zinc-selenium tea were the first to explore the effect of tea on the cardiotoxicity of rats caused by NP exposure, and then to compare the intervention of zinc-selenium tea and ordinary green tea. The aim of this study was to explore whether zinc-selenium tea can interfere with the cardiotoxicity caused by NP, for providing qualitative scientific basis for relieving the cardiotoxicity induced by NP.…”