Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Consolare Valeria, 98100 Messina, Italy.
Int J Mol Sci. 2023 Jul 15;24(14):11510. doi: 10.3390/ijms241411510.
Myocarditis is an inflammatory cardiac disorder and the primary cause of heart failure in young adults. Its origins can be attributed to various factors, including bacterial or viral infections, exposure to toxins or drugs, endocrine disruptors (EDs), and autoimmune processes. Tebuconazole (TEB), which is a member of the triazole fungicide family, is utilized to safeguard agricultural crop plants against fungal pathogens. Although TEB poses serious threats to mammal health, the information about how it induces toxic effects through various pathways, particularly in autoimmune diseases, are still limited. Thus, the aim of this paper was to evaluate the effect of TEB exposure in autoimmune myocarditis (AM). To induce AM, rats were immunized with porcine cardiac myosin and exposed to TEB for 21 days. Thereafter, animals were sacrificed, and histological, biochemical, and molecular analyses were performed. TEB exposure increased heart weight, systolic blood pressure and heart rate already augmented by AM. Additionally, it significantly increased creatine phosphokinase heart (CK-MB), creatine phosphokinase (CPK), cardiac troponin T (cTnT), and cardiac troponin I (cTnI), as compared to the control. From the histological perspective, TEB exacerbates the histological damage induced by AM (necrosis, inflammation and cell infiltration) and increased fibrosis and collagen deposition. TEB exposure strongly increased pro-inflammatory cytokines and prooxidant levels (O2, HO, NO, lipid peroxidation) and reduced antioxidant enzyme levels, which were already dysregulated by AM. Additionally, TEB increased NOX-4 expression and the TGFβ1-Smads pathway already activated by AM. Overall, our results showed that TEB exposure strongly aggravated the cardiotoxicity induced by AM.
心肌炎是一种炎症性心脏疾病，也是年轻人心力衰竭的主要原因。其病因可归因于多种因素，包括细菌或病毒感染、接触毒素或药物、内分泌干扰物（EDs）和自身免疫过程。特比萘芬（TEB）是三唑类杀真菌剂家族的一员，用于保护农业作物植物免受真菌病原体的侵害。尽管 TEB 对哺乳动物健康构成严重威胁，但关于它如何通过各种途径（特别是在自身免疫性疾病中）引起毒性作用的信息仍然有限。因此，本文旨在评估 TEB 暴露对自身免疫性心肌炎（AM）的影响。为了诱导 AM，用猪心肌肌球蛋白免疫大鼠，并暴露于 TEB 21 天。然后处死动物，并进行组织学、生化和分子分析。TEB 暴露增加了心脏重量、收缩压和 AM 已经升高的心率。此外，与对照组相比，它还显著增加了肌酸磷酸激酶心脏（CK-MB）、肌酸磷酸激酶（CPK）、心肌肌钙蛋白 T（cTnT）和心肌肌钙蛋白 I（cTnI）。从组织学角度来看，TEB 加剧了 AM 引起的组织损伤（坏死、炎症和细胞浸润），并增加了纤维化和胶原蛋白沉积。TEB 暴露强烈增加了促炎细胞因子和促氧化剂水平（O2、HO、NO、脂质过氧化），并降低了 AM 已经失调的抗氧化酶水平。此外，TEB 增加了 NOX-4 表达和 AM 已经激活的 TGFβ1-Smads 途径。总体而言，我们的结果表明，TEB 暴露强烈加剧了 AM 引起的心脏毒性。
