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 (P < 0.05). 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.

Unravelling the ageing-reversal potency of stem cell-derived extracellular vesicles in a rat model of premature cardiac senescence

“…However, we did confirm our hypothesis by demonstrating a more favorable therapeutic profile of the P-EVs vs. NP-EVs in other genetic and structural parameters where the model worked appropriately, although the degree of these changes was still far from the described in naturally-aged animals Grigorian-Shamagian et al, 2017;Liao et al, 2015;Liu et al, 2021). On the other hand, although the number of human donors included in our study was not small (n=18) and the chronological age range was wide (3 months -81 years old), larger sample size, and inclusion of neonate samples, would permit to make a more robust conclusion about the implication of the chronological age of the donors on the potency of the therapeutic product, absent in this study.…”

Nigella sativa seeds mitigate the hepatic histo-architectural and ultrastructural changes induced by 4-nonylphenol in Clarias gariepinus

“…The upregulation of collagen expression is responsible for the excessive fibrosis surrounding the central veins and bile pathway in the 4-NP-exposed group 46 . The impeded intrahepatic perfusion, secondary to fibrosis, stimulates advanced fibrogenesis and subsequent portal hypertension 47 .…”