Ruthenium Red

Ruthenium Red is a selective Transient receptor potential vanilloid-4 (TRPV4) antagonist with an IC₅₀ of 86nM ^[1]. Ruthenium Red is also an antagonist of arginine deiminase/peptidylarginine deiminase (PAD)^[2]. Ruthenium Red is a polycationic dye that can be used to visualize cells, tissues, and nutrient bacteria^[3]. Additionally, Ruthenium Red has been shown to inhibit tumor development^[4]

In vitro, pre-treatment of human peripheral blood lymphocytes (PBLs) with Ruthenium Red (100nM–1µM), followed by stimulation with herpes simplex virus (HSV) antigens (10⁵ PBLs per well, 200µL total volume) or mitomycin C-treated donor cells (10⁵ cells per well, as stimulator cells) for 3–5 days, significantly inhibits T-cell proliferation and reduces the immune response^[5]. Pre-treatment of mouse bone marrow-derived macrophages (BMMs) with Ruthenium Red (0.375–1.5µM), followed by stimulation with RANKL (50ng/mL) for 5–7 days, significantly inhibits the formation of TRAP-positive multinucleated osteoclasts and reduces the bone resorption function of osteoclasts^[6].

In vivo, Ruthenium Red (60µg/kg) was administered intraperitoneally alone or in combination with Melatonin (10mg/kg) to Wistar rats. Ruthenium Red significantly reduced the activity of mitochondrial respiratory complexes I and IV and also significantly decreased the activity of glutathione peroxidase (GPx)^[7]. Ruthenium Red (10⁻⁸–10⁻⁶mol/site) was administered by intradermal injection to New Zealand white rabbits, and Ruthenium Red significantly inhibited capsaicin-induced edema and increased blood flow in a dose-dependent manner^[8].

References:
[1] Kumar M, Zaman MK, Das S, et al. Transient Receptor Potential Vanilloid (TRPV4) channel inhibition: A novel promising approach for the treatment of lung diseases. Biomed Pharmacother. 2023 Jul;163:114861.
[2] Sarnik J, Makowska JS. Highlighting the versatility of the citrullination process. Immunobiology. 2022 Jul;227(4):152233.
[3] Dierichs R. Ruthenium red as a stain for electron microscopy. Some new aspects of its application and mode of action. Histochemistry. 1979 Nov;64(2):171-87.
[4] Anghileri LJ. The in vivo inhibition of tumor growth by ruthenium red: its relationship with the metabolism of calcium in the tumor. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1975;83(3):213-7.
[5] Dwyer DS, Gordon K, Jones B. Ruthenium Red potently inhibits immune responses both in vitro and in vivo. Int J Immunopharmacol. 1995 Nov;17(11):931-40.
[6] Wang Y, Li X, Zhou S, et al. MCU Inhibitor Ruthenium Red Alleviates the Osteoclastogenesis and Ovariectomized Osteoporosis via Suppressing RANKL-Induced ROS Production and NFATc1 Activation through P38 MAPK Signaling Pathway. Oxid Med Cell Longev. 2022 Sep 13;2022:7727006.
[7] Martín M, Macías M, Escames G, et al. Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res. 2000 May;28(4):242-8.
[8] Buckley TL, Brain SD, Williams TJ. Ruthenium red selectively inhibits oedema formation and increased blood flow induced by capsaicin in rabbit skin. Br J Pharmacol. 1990 Jan;99(1):7-8.

Ruthenium Red是一种选择性Transient receptor potential vanilloid-4（TRPV4）拮抗剂，IC₅₀为86nM^[1]，Ruthenium Red也是精氨酸脱亚胺酶/肽精氨酸脱亚胺酶（PAD）的拮抗剂^[2]。Ruthenium Red还是一种聚阳离子染料，可用于观察细胞、组织和营养细菌^[3]。此外，Ruthenium Red还具抑制肿瘤发育的作用^[4]。

在体外，Ruthenium Red（100nM–1µM）预处理人外周血淋巴细胞（PBLs），随后以单纯疱疹病毒（HSV）抗原（10⁵ PBLs/孔，200µL总体积）或经丝裂霉素C处理的供体细胞（10⁵细胞/孔，作为刺激细胞）刺激3–5天，Ruthenium Red显著抑制T细胞增殖，同时降低免疫反应^[5]。Ruthenium Red（0.375–1.5µM）预处理小鼠骨髓来源的巨噬细胞（BMMs），随后以RANKL（50ng/mL）刺激5–7天，显著抑制TRAP阳性多核破骨细胞的形成，同时降低破骨细胞的骨吸收功能^[6]。

在体内，Ruthenium Red（60µg/kg）单独腹腔注射，或与Melatonin（10mg/kg）联合腹腔注射，用于处理Wistar大鼠。Ruthenium Red能够显著抑制呼吸链复合体I和IV的活性，Ruthenium Red还显著降低了谷胱甘肽过氧化物酶（GPx）的活性 ^[7]。Ruthenium Red（10⁻⁸–10⁻⁶ mol/site）通过皮内注射，用于处理新西兰白兔。Ruthenium Red以剂量依赖性方式显著抑制由辣椒素诱导的皮肤水肿和血流增加^[8]。