Hypermethioninemia is a disorder characterized by high plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO). Studies have reported associated inflammatory complications, but the mechanisms involved in the pathophysiology of hypermethioninemia are still uncertain. The present study aims to evaluate the effect of chronic administration of Met and/or MetO on phenotypic characteristics of macrophages, in addition to oxidative stress, purinergic system, and inflammatory mediators in macrophages. In this study, Swiss male mice were subcutaneously injected with Met and MetO at concentrations of 0.35–1.2 g/kg body weight and 0.09–0.3 g/kg body weight, respectively, from the 10th–38th day post-birth, while the control group was treated with saline solution. The results revealed that Met and/or MetO induce an M1/classical activation phenotype associated with increased levels of tumor necrosis factor alpha and nitrite, and reduced arginase activity. It was also found that Met and/or MetO alter the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as the levels of thiol and reactive oxygen species in macrophages. The chronic administration of Met and/or MetO also promotes alteration in the hydrolysis of ATP and ADP, as indicated by the increased activity of ectonucleotidases. These results demonstrate that chronic administration of Met and/or MetO promotes activated pro-inflammatory profile by inducing M1/classical macrophage polarization. Thus, the changes in redox status and purinergic system upon chronic Met and/or MetO exposure may contribute towards better understanding of the alterations consistent with hypermethioninemic patients.

中文翻译：

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长期用蛋氨酸和蛋氨酸亚砜治疗小鼠巨噬细胞表型，氧化还原和嘌呤能反应的特征。

高蛋氨酸血症是一种以血浆高水平的蛋氨酸（Met）及其代谢产物（如蛋氨酸亚砜（MetO））为特征的疾病。研究已经报道了相关的炎症并发症，但是高蛋氨酸血症的病理生理机制尚不清楚。本研究旨在评估长期施用Met和/或MetO对巨噬细胞表型特征以及氧化应激，嘌呤能系统和巨噬细胞炎症介质的影响。在这项研究中，从出生后第10-38天开始，对瑞士雄性小鼠皮下注射Met和MetO，其浓度分别为0.35-1.2 g / kg体重和0.09-0.3 g / kg体重。本组用盐溶液治疗。结果表明，Met和/或MetO诱导了M1 /经典激活表型，与肿瘤坏死因子α和亚硝酸盐水平增加和精氨酸酶活性降低有关。还发现Met和/或MetO改变了抗氧化剂酶超氧化物歧化酶，过氧化氢酶和谷胱甘肽过氧化物酶的活性，以及​​巨噬细胞中硫醇和活性氧的含量。Met和/或MetO的长期给药还可以促进ATP和ADP水解的改变，如外切核苷酸酶活性的增加所表明的。这些结果表明，Met和/或MetO的长期给药可通过诱导M1 /经典巨噬细胞极化来促进活化的促炎特性。从而，