当前位置: X-MOL 学术Hum. Exp. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Synthesis of N,N'-bis(1,5-dimethyl-2-phenyl-1,2-dihydro-3-oxopyrazol-4-yl) sebacamide that ameliorate osteoarthritis symptoms and improve bone marrow matrix structure and cartilage alterations induced by monoiodoacetate in the rat model: "Suggested potent anti-inflammatory agent against COVID-19".
Human & Experimental Toxicology ( IF 2.8 ) Pub Date : 2020-08-25 , DOI: 10.1177/0960327120945779
M S Refat 1, 2 , R Z Hamza 3, 4 , Ama Adam 1 , H A Saad 1, 5 , A A Gobouri 1 , F A Al-Salmi 3 , T Altalhi 1 , S M El-Megharbel 1, 5
Affiliation  

To assess the chondroprotective effect and influence of N,N′-bis(1,5-dimethyl-2-phenyl-1,2-dihydro-3-oxopyrazol-4-yl) sebacamide (dpdo) that was synthesized through the reaction of phenazone with sebacoyl chloride and screened for its biological activity especially as anti-arthritic and anti-inflammatory agent in a monoiodoacetate (MA)-induced experimental osteoarthritis (OA) model. Thirty male albino rats weighing “190–200 g” were divided randomly into three groups (10 each): control, MA-induced OA, and MA-induced OA + dpdo. In MA-induced OA rat, the tumor necrosis factor alpha, interleukin 6, C-reactive protein, rheumatoid factors, reactive oxygen species, as well as all the mitochondrial markers such as mitochondria membrane potential, swelling mitochondria, cytochrome c oxidase (complex IV), and serum oxidative/antioxidant status (malondialdehyde level and activities of myeloperoxidase and xanthine oxidase) are elevated. Also, the activity of succinate dehydrogenase (complex II), levels of ATP, the level of glutathione (GSH), and thiol were markedly diminished in the MA-induced OA group compared to the normal control rats. These findings showed that mitochondrial function is associated with OA pathophysiological alterations and high gene expressions of (IL-6, TNF-a, and IL-1b) and suggests a promising use of dpdo as potential ameliorative agents in the animal model of OA and could act as anti-inflammatory agent in case of severe infection with COVID-19. It is clearly appeared in improving the bone cortex and bone marrow in the treated group with the novel compound in histological and transmission electron microscopic sections which is a very important issue today in fighting severe infections that have significant effects on the blood indices and declining of blood corpuscles like COVID-19, in addition to declining the genotoxicity and inflammation induced by MA in male rats. The novel synthesized compound was highly effective in improving all the above mentioned parameters.



中文翻译:

N,N'-双(1,5-二甲基-2-苯基-1,2-二氢-3-氧并吡唑-4-基)癸二酰胺的合成,可减轻骨关节炎的症状并改善骨髓基质结构和单碘乙酸酯诱导的软骨改变在大鼠模型中:“建议针对COVID-19的有效抗炎药”。

为了评估N的软骨保护作用和影响,N'-双(1,5-二甲基-2-苯基-1,2-二氢-3-氧吡唑并-4-基)癸二酰胺(dpdo)是通过苯乙酮与癸二酰氯的混合物,并筛选其生物活性,尤其是在单碘乙酸酯(MA)诱导的实验性骨关节炎(OA)模型中作为抗关节炎药和抗炎药。将30只体重为“ 190–200 g”的白化病雄性大鼠随机分为三组(每组10只):对照组,MA诱导的OA和MA诱导的OA + dpdo。在MA诱导的OA大鼠中,肿瘤坏死因子α,白介素6,C反应蛋白,类风湿因子,活性氧以及所有线粒体标志物,例如线粒体膜电位,肿胀线粒体,细胞色素C氧化酶(复合物IV)和血清氧化/抗氧化剂状态(丙二醛水平以及髓过氧化物酶和黄嘌呤氧化酶的活性)升高。此外,与正常对照组相比,MA诱导的OA组的琥珀酸脱氢酶(复合物II)的活性,ATP的水平,谷胱甘肽(GSH)的水平和硫醇的水平明显降低。这些发现表明线粒体功能与OA病理生理改变和(IL-6,TNF-a和IL-1b)高基因表达有关,并暗示dpdo在OA动物模型中有望用作潜在的改良剂,并且可能在严重感染COVID-19时起抗炎剂的作用。在组织学和透射电镜切片中,使用该新型化合物改善了治疗组的骨皮质和骨髓,这显然已成为当今对抗严重感染的重要问题,这些感染对血液指标和血液下降具有重大影响除了降低雄性大鼠中MA引起的遗传毒性和炎症外,还出现了COVID-19等小体。该新型合成化合物在改善所有上述参数方面非常有效。

更新日期:2020-08-25
down
wechat
bug