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Hum Exp Toxicol ; 40(2): 325-341, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1067095


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.

Anti-Inflammatory Agents/therapeutic use , COVID-19 Drug Treatment , Osteoarthritis/drug therapy , SARS-CoV-2 , Adenosine Triphosphate/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Bone and Bones/drug effects , Bone and Bones/pathology , Bone and Bones/ultrastructure , C-Reactive Protein/analysis , Cytochromes c/metabolism , Cytokines/metabolism , Disease Models, Animal , Glutathione/metabolism , Iodoacetic Acid , Lipid Peroxidation/drug effects , Male , Matrix Metalloproteinases/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/physiology , Osteoarthritis/chemically induced , Osteoarthritis/metabolism , Osteoarthritis/pathology , Rats , Reactive Oxygen Species/metabolism , Succinate Dehydrogenase/metabolism