通过解偶联氧化磷酸化,2,4-二硝基苯酚(DNP)减弱活性氧(ROS)的生物合成,已知会加重恰加斯病中的感染性心肌炎。因此,研究了以DNP为基础的化疗对克氏锥虫诱导的急性心肌炎的影响。C56BL/6小鼠未感染和未治疗的感染,每天用100mg/kg苯并硝唑治疗(Bz,参考药物),在确认克氏毛虫感染后,通过管饲法研究了5和10mg/kg的DNP,持续11天。在最后一次治疗24小时后,对动物实施安乐死,并收集心脏进行微结构,免疫学和生化分析。克氏杆菌接种诱导的全身性炎症(例如,细胞因子和抗T.CruziIgG上调),心脏感染(T.克鲁兹DNA),氧化应激,未经治疗的小鼠的炎症浸润和微观心肌损伤。DNP治疗加重了心脏感染和微结构损伤,Bz明显减弱。DNP(10mg/kg)也可有效减弱ROS(总ROS,H2O2和O2-),一氧化氮(NO),脂质(丙二醛-MDA)和蛋白质(蛋白质羰基-PCn)氧化,TNF,IFN-γ,IL-10和MCP-1/CCL2,抗T。克鲁兹IgG,心肌肌钙蛋白I水平,以及感染克氏杆菌的小鼠的炎症浸润和心脏损伤。我们的发现表明DNP加重了感染小鼠的心脏感染和微观结构心肌细胞损伤。这些反应与DNP的抗氧化和抗炎特性有关,通过削弱受感染宿主的促氧化剂和促炎保护机制来促进感染。相反,Bz诱导的心脏保护作用结合有效的抗炎和抗寄生虫反应,防止心脏感染,查加斯病中的氧化应激和微观结构损伤。
By uncoupling oxidative phosphorylation, 2,4-dinitrophenol (DNP) attenuates reactive oxygen species (ROS) biosynthesis, which are known to aggravate infectious myocarditis in Chagas disease. Thus, the impact of DNP-based chemotherapy on Trypanosoma cruzi-induced acute myocarditis was investigated. C56BL/6 mice uninfected and infected untreated and treated daily with 100 mg/kg benznidazole (Bz, reference drug), 5 and 10 mg/kg DNP by gavage for 11 days after confirmation of T. cruzi infection were investigated. Twenty-four hours after the last treatment, the animals were euthanized and the heart was collected for microstructural, immunological and biochemical analyses. T. cruzi inoculation induced systemic inflammation (e.g., cytokines and anti-T. cruzi IgG upregulation), cardiac infection (T. cruzi DNA), oxidative stress, inflammatory infiltrate and microstructural myocardial damage in untreated mice. DNP treatment aggravated heart infection and microstructural damage, which were markedly attenuated by Bz. DNP (10 mg/kg) was also effective in attenuating ROS (total ROS, H2O2, and O2-), nitric oxide (NO), lipid (malondialdehyde - MDA) and protein (protein carbonyl - PCn) oxidation, TNF, IFN-γ, IL-10, and MCP-1/CCL2, anti-T. cruzi IgG, cardiac troponin I levels, as well as inflammatory infiltrate and cardiac damage in T. cruzi-infected mice. Our findings indicate that DNP aggravated heart infection and microstructural cardiomyocytes damage in infected mice. These responses were related to the antioxidant and anti-inflammatory properties of DNP, which favors infection by weakening the pro-oxidant and pro-inflammatory protective mechanisms of the infected host. Conversely, Bz-induced cardioprotective effects combined effective anti-inflammatory and antiparasitic responses, which protect against heart infection, oxidative stress, and microstructural damage in Chagas disease.