ABSTRACT
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.
Subject(s)
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/metabolismABSTRACT
Four new complexes of Hg (II), Pb (II), Sn (II) and Bi (III) with indomethacin drug ligand (IMC) were synthesized and characterized by using infrared, electronic, 1H-NMR spectral, thermogravimetric and conductivity measurements. The IMC was found to act as bidentate chelating agent. IMC complexes coordinate through the oxygen of the carboxyl group. The molar ratio chelation is 1:2 (M2+:IMC) with general formula [M (IMC) 2], nH2O for Hg (II), Pb(II) and Sn(II), but 1:3 for Bi(III) ions. Antibacterial screening of these heavy metal complexes against Escherichia coli (Gram-ve), Bacillus subtilis (Gram +ve) and anti-fungi (Asperagillus oryzae, Asperagillus niger, Asperagillus Flavus) were investigated. In the present study, we found evidence suggesting that Bi+3/IMC possesses the capacity to protect the stomach, sperm, testes, cellular ATP, cellular NAD, INSL3, PGD2, PGE2 and antioxidant enzymes from deleterious actions of IMC.
Subject(s)
Anti-Bacterial Agents , Bacteria/growth & development , Gastric Mucosa/metabolism , Indomethacin , Metals, Heavy , Oxidative Stress/drug effects , Reproduction/drug effects , Testis/metabolism , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Indomethacin/analogs & derivatives , Indomethacin/chemical synthesis , Indomethacin/chemistry , Indomethacin/pharmacology , Male , Metals, Heavy/chemistry , Metals, Heavy/pharmacology , Rats , Rats, WistarABSTRACT
Compounds having general formula: [M(FO)(Cl)x(H2O)y]x zH2O, where (M=Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II), FO=folate anion, x=2 or 4, y=2 or 4 and z=0, 1, 2, 3, 5 or 15) were prepared. The obtained compounds were characterized by elemental analysis, infrared as well as electronic spectra, thermogravimetric analysis and the conductivity measurements. The results suggested that all folate complexes were formed by 2:1 molar ratio (metal:folic acid) as a bidentate through both of the two carboxylic groups. The molar conductance measurements proved that the folate complexes are electrolytes. The kinetic thermodynamic parameters such as: E*, DeltaH*, DeltaS* and DeltaG* were estimated from the DTG curves. The antibacterial evaluation of the folic acid and their complexes was also done against some Gram positive/negative bacteria as well as fungi.
