Gomes Antony, Saha Partha Pratim, Bhowmik Tanmoy, Dasgupta Anjan Kumar, Dasgupta Subir Chandra
Department of Physiology, Laboratory of Toxinology & Experimental Pharmacodynamics, University of Calcutta, Kolkata, India.
Department of Biochemistry, University of Calcutta, Kolkata, India.
Indian J Med Res. 2016 Dec;144(6):910-917. doi: 10.4103/ijmr.IJMR_1078_14.
BACKGROUND & OBJECTIVES: Increased severity of osteoarthritis (OA) and adverse side effects of its treatment led to the search for alternative therapies. It was previously reported that snake venom protein toxin Naja kaouthia cytotoxin 1 (NKCT1) and gold nanoparticle (GNP) individually have potential against excremental arthritis. In this study, we analyzed the protective activity of GNP conjugated protein toxin NKCT1 (GNP-NKCT1) against experimental OA.
Gold nanoparticle conjugation with NKCT1 (GNP-NKCT1) was done and its physiochemical properties were studied. OA was induced in male albino rats by intra-articular injection of bacterial collagenase and treatment was done with NKCT1/GNP-NKCT1/standard drug (indomethacin). Physical parameter (ankle diameter), urinary markers (hydroxyproline, glucosamine, pyridinoline, deoxypyridinoline), serum and synovial membrane pro-inflammatory markers [tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-17, vascular endothelial growth factor (VEGF)] and matrix metalloproteinase 1 (MMP1) were measured. Joint histopathology and scanning electron microscopy imaging of articular cartilage surface were also done.
Physical parameters, urinary markers, serum and synovial membrane pro-inflammatory makers and MMP1 were increased in arthritic rats and significantly restored after GNP-NKCT1/NKCT1 treatment. Joint histopathology and scanning electron microscopy imaging of articular cartilage surface also indicated the protective effect of GNP-NKCT1 against inflammatory response and cartilage degradation in osteoarthritic rats.
INTERPRETATION & CONCLUSIONS: In this study restoration of the arthritic markers and bone degradation by GNP-NKCT1 treatment indicated the anti-osteoarthritic property of GNP-NKCT1. Further studies need to be done to confirm these findings.
骨关节炎（OA）病情加重及其治疗的不良副作用促使人们寻找替代疗法。此前有报道称，蛇毒蛋白毒素眼镜王蛇细胞毒素1（NKCT1）和金纳米颗粒（GNP）各自对实验性关节炎具有潜在作用。在本研究中，我们分析了GNP偶联蛋白毒素NKCT1（GNP-NKCT1）对实验性OA的保护活性。
将NKCT1与金纳米颗粒偶联制成GNP-NKCT1，并研究其理化性质。通过关节腔内注射细菌胶原酶诱导雄性白化大鼠患OA，并用NKCT1/GNP-NKCT1/标准药物（吲哚美辛）进行治疗。测量物理参数（踝关节直径）、尿液标志物（羟脯氨酸、氨基葡萄糖、吡啶啉、脱氧吡啶啉）、血清和滑膜促炎标志物[肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、IL-17、血管内皮生长因子（VEGF）]以及基质金属蛋白酶1（MMP1）。还进行了关节组织病理学检查和关节软骨表面的扫描电子显微镜成像。
关节炎大鼠的物理参数、尿液标志物、血清和滑膜促炎标志物以及MMP1均升高，经GNP-NKCT1/NKCT1治疗后显著恢复。关节组织病理学检查和关节软骨表面的扫描电子显微镜成像也表明，GNP-NKCT1对骨关节炎大鼠的炎症反应和软骨降解具有保护作用。
在本研究中，GNP-NKCT1治疗使关节炎标志物恢复正常并减轻了骨降解，表明GNP-NKCT1具有抗骨关节炎特性。需要进一步研究以证实这些发现。
