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一种新型的阳离子钯(II)二硫代氨基甲酸盐通过抑制体内模型中的炎症介质表现出抗炎、镇痛和解热活性。

A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models.

机构信息

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2019 Aug;392(8):961-977. doi: 10.1007/s00210-019-01645-y. Epub 2019 Apr 9.

Abstract

Inflammation is being a protective mechanism of the body towards the injury. However, chronic and progressive inflammation may lead to some chronic diseases. Due to the serious unwanted effects associated with available drugs, new and safe anti-inflammatory agents are still required. Therefore, the present study was designed to investigate the anti-inflammatory, analgesics, and antipyretic properties of a new compound (4-benzylpiperidine-1-carbodithioato-κS,S')(1,4-bis-(diphenylphosphino)butane)palladium(II)chloride monohydrate (compound-1) in albino mice models. Compound-1 was characterized by elemental analysis, FT-IR, and multinuclear NMR spectroscopy. Initially, compound-1 was evaluated for cytotoxicity, anti-inflammatory, and analgesic activities by performing MTT assay, carrageenan-, histamine-, serotonin-, and CFA-induced paw edema, mechanical hyperalgesia, thermal hyperalgesia, and mechanical allodynia (0.1, 1, and 10 mg/kg, b.w). Antipyretic activity was evaluated in brewer's yeast-induced model. The pro-inflammatory cytokines were measured by using commercially available ELISA kits. Additionally, nitrite production, antioxidant enzymes, H&E staining, muscle activity and motor coordination, and kidney and liver function tests were also determined. The results demonstrated that compound-1 significantly inhibited inflammation, pain, and febrile responses in all models at a dose of 10 mg/kg without effecting viability of cells in vitro at concentrations up to 100 μM. Similarly, the data clearly demonstrated significant reduction in the pro-inflammatory cytokines and nitrite production while enhancing antioxidant enzymes. Furthermore, pretreatment with compound-1 did not produce any prominent side effect on kidney, liver, stomach, and muscles. These findings suggest that compound-1 has potent anti-inflammatory-, pain-, and pyrexia-relieving properties. Hence, compound-1 might be a potential candidate for the therapeutic management of chronic inflammation and pain.

摘要

炎症是身体对损伤的一种保护机制。然而,慢性和进行性炎症可能导致一些慢性疾病。由于现有药物相关的严重不良反应,仍然需要新的安全的抗炎药物。因此,本研究旨在研究一种新化合物(4-苄基哌啶-1-碳二硫代酸-κS,S')(1,4-双-(二苯基膦)丁烷)钯(II)氯化物一水合物(化合物-1)在白化小鼠模型中的抗炎、镇痛和退热特性。通过元素分析、FT-IR 和多核 NMR 光谱对化合物-1 进行了表征。首先,通过 MTT 测定法、角叉菜胶、组胺、血清素和 CFA 诱导的爪肿胀、机械性痛觉过敏、热痛觉过敏和机械性感觉异常(0.1、1 和 10mg/kg,bw)来评估化合物-1 的细胞毒性、抗炎和镇痛活性。在啤酒酵母诱导的模型中评估了退热活性。使用市售的 ELISA 试剂盒测量促炎细胞因子。此外,还测定了亚硝酸盐的产生、抗氧化酶、H&E 染色、肌肉活动和运动协调以及肾功能和肝功能试验。结果表明,化合物-1 在 10mg/kg 剂量下显著抑制所有模型中的炎症、疼痛和发热反应,而在高达 100μM 的浓度下对体外细胞活力没有影响。同样,数据清楚地表明,促炎细胞因子和亚硝酸盐的产生显著减少,而抗氧化酶显著增加。此外,化合物-1 的预处理对肾脏、肝脏、胃和肌肉没有产生任何明显的副作用。这些发现表明化合物-1 具有强大的抗炎、止痛和退热特性。因此,化合物-1 可能是治疗慢性炎症和疼痛的潜在候选药物。

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