Reducing inflammation is a promising therapeutic approach for sepsis-induced cardiomyopathy (SIC). The 5-Methoxytryptophan (5-MTP) is a tryptophan metabolite that demonstrates anti-inflammatory, anti-fibrosis, anti-tumorigenesis, and anti-senescence features. Current investigations aimed to assess the 5-MTP pretreatment impacts on lipopolysaccharide (LPS)-induced cardiac injury and dysfunction. For in vivo studies, the mice were categorized randomly into four groups: control, LPS, LPS+5-MTP (25 mg/kg) and LPS+5-MTP (50 mg/kg). The mice in the LPS+5-MTP groups were given 5-MTP intraperitoneally once a day for 7 days. LPS (10 mg/kg) was then administered intraperitoneally for 24 h. Echocardiography, cardiac injury biomarkers, and H & E staining evaluated heart anatomy and function. The findings indicate that 5-MTP pretreatment significantly reduced LPS-induced heart dysfunction and morphological alterations. Western blot assay was used for investigating molecular mechanisms. After LPS stimulation, the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) protein levels increased while anti-inflammatory cytokine (IL-10) decreased; however, 5-MTP pretreatment mitigated this response by suppressing the stimulation of the NF-κB signaling pathway. Furthermore, 5-MTP administration reduced LPS-induced cardiac apoptosis, as demonstrated by increased protein levels of cleaved-Casepase-1, cleaved-Casepase-3 and Bax, and decreased protein level of Bcl-2 after LPS stimulation, whereas LPS-induced cardiac apoptosis was reversed by 5-MTP pretreatment. In vitro, 5-MTP pretreatment had a similar cardioprotective effect on cultured cardiac fibroblasts challenged with LPS. In conclusion, 5-MTP pretreatment can reduce LPS-induced cardiac inflammation and apoptosis, implying that 5-MTP is a possible therapeutic option for SIC.

中文翻译：

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5-甲氧基色氨酸预处理减轻脂多糖诱导的心脏损伤和功能障碍

减轻炎症是脓毒症诱发的心肌病 (SIC) 的一种有前途的治疗方法。5-甲氧基色氨酸 (5-MTP) 是一种色氨酸代谢物，具有抗炎、抗纤维化、抗肿瘤发生和抗衰老的特性。目前的研究旨在评估 5-MTP 预处理对脂多糖 (LPS) 诱导的心脏损伤和功能障碍的影响。对于体内研究，将小鼠随机分为四组：对照、LPS、LPS+5-MTP (25 mg/kg) 和 LPS+5-MTP (50 mg/kg)。LPS+5-MTP组小鼠每天一次腹腔注射5-MTP，连续7天。然后腹膜内施用 LPS (10 mg/kg) 24 小时。超声心动图、心脏损伤生物标志物和 H & E 染色评估心脏解剖和功能。研究结果表明，5-MTP 预处理显着降低了 LPS 诱导的心脏功能障碍和形态学改变。蛋白质印迹分析用于研究分子机制。LPS刺激后，促炎细胞因子（IL-1β、IL-6、TNF-α和NLRP3）蛋白水平升高，而抗炎细胞因子（IL-10）降低；然而，5-MTP 预处理通过抑制 NF-κB 信号通路的刺激来减轻这种反应。此外，5-MTP 给药减少了 LPS 诱导的心脏细胞凋亡，如 LPS 刺激后 cleaved-Casepase-1、cleaved-Casepase-3 和 Bax 的蛋白质水平增加以及 Bcl-2 的蛋白质水平降低所证明的，而 LPS 诱导5-MTP 预处理可逆转心脏细胞凋亡。体外，5-MTP 预处理对用 LPS 攻击的培养的心脏成纤维细胞具有类似的心脏保护作用。总之，5-MTP 预处理可以减少 LPS 诱导的心脏炎症和细胞凋亡，这意味着 5-MTP 是 SIC 的一种可能的治疗选择。