Poradowski Dominik, Chrószcz Aleksander, Spychaj Radosław, Wolińska Joanna, Onar Vedat
Department of Biostructure and Animal Physiology, Division of Animal Anatomy, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Kożuchowska 1, 51-631 Wrocław, Poland.
Department of Fermentation and Cereals Technology, Faculty of Biotechnology and Food Science, Wroclaw University of Environmental and Life Sciences, J. Chełmońskiego 37, 51-630 Wrocław, Poland.
Biomedicines. 2024 Aug 15;12(8):1869. doi: 10.3390/biomedicines12081869.
The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC-over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bisphosphonate commonly used in orthopaedic and metabolic diseases of the musculoskeletal system, including hypercalcemia, postmenopausal osteoporosis, Paget's disease, etc. The aim of this study was to check whether there were any pharmacological interactions between metamizole and risedronate sodium in in vitro studies. Cell viability was assessed using the MTT method, the number of apoptotic cells was assessed using the labelling TUNEL method, and the cell cycle assessment was performed with a flow cytometer and propidium iodide. This was a pilot study, which is why only two cancer cell lines were tested: D-17 of canine osteosarcoma and U-2 OS of human osteosarcoma. Exposure of the canine osteosarcoma cell line to a combination of risedronate sodium (100 µg/mL) and metamizole (50, 5, and 0.5 µg/mL) resulted in the complete abolition of the cytoprotective activity of metamizole. In the human osteosarcoma cell line, the cytotoxic effect of risedronate sodium was entirely eliminated in the presence of 50 µg/mL of metamizole. The cytoprotective and anti-apoptotic effect of metamizole in combination with risedronate sodium in the tested human and canine osteosarcoma cell lines indicates an urgent need for further in vivo studies to confirm or disprove the potential dose-dependent undesirable effect of such a therapy.
安乃近在世界各地的可获得性差异很大。在美国、英国或澳大利亚等国家，安乃近的使用被完全禁止，也有一些国家该药物仅凭处方可用（如希腊、意大利、西班牙等），还有一些国家它是非处方药（如大多数亚洲和南美国家）。安乃近作为一种具有强效镇痛作用的药物，可单独或与阿片类药物联合用作其他非甾体抗炎药的替代品。利塞膦酸钠是第三代双膦酸盐，常用于肌肉骨骼系统的骨科和代谢性疾病，包括高钙血症、绝经后骨质疏松症、佩吉特病等。本研究的目的是在体外研究中检测安乃近和利塞膦酸钠之间是否存在任何药物相互作用。使用MTT法评估细胞活力，使用TUNEL标记法评估凋亡细胞数量，并通过流式细胞仪和碘化丙啶进行细胞周期评估。这是一项初步研究，因此仅测试了两种癌细胞系：犬骨肉瘤的D - 17和人骨肉瘤的U - 2 OS。犬骨肉瘤细胞系暴露于利塞膦酸钠（100 µg/mL）和安乃近（50、5和0.5 µg/mL）的组合中导致安乃近的细胞保护活性完全丧失。在人骨肉瘤细胞系中，在存在50 µg/mL安乃近的情况下，利塞膦酸钠的细胞毒性作用被完全消除。在测试的人骨肉瘤和犬骨肉瘤细胞系中，安乃近与利塞膦酸钠联合使用时的细胞保护和抗凋亡作用表明迫切需要进一步的体内研究，以证实或反驳这种治疗潜在的剂量依赖性不良影响。
