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".

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.

Synergistic antioxidant capacities of vanillin and chitosan nanoparticles against reactive oxygen species, hepatotoxicity, and genotoxicity induced by aging in male Wistar rats.

This study aimed to evaluate the synergistic effects of both vanillin (V) and chitosan nanoparticles (CNPs) in alleviating hepatotoxicity, oxidative injury, and genotoxicity induced by d-galactose (DG) and resulted from aging in male albino rats. Male Wistar rats were divided into seven groups (10 rats/group) as follows: control group, (DG) group (100 mg/kg), (V) group (100 mg/kg), CNPs either (low dose (LD) or CNPs (high dose (HD) (140 mg/kg) and (280 mg/kg), and CNPs (LD and HD) dose with V- and DG plus V-treated groups. The CNPs were characterized by transmission electron microscopy (TEM), zeta potential, and size distribution of nanoparticles. After 60 consecutive days of exposure, some biochemical parameters were measured as hepatic aminotransferases enzymes, lipid profile, tumor necrosis factor alpha, interleukin-6 (IL-6), markers of inflammation, tissue damage lactate dehydrogenase, C-reactive protein (CRP), mitochondrial potential activities, myeloperoxidase, xanthine oxidase, CRP, succinate dehydrogenase, mitochondria membrane potential, malondialdehyde levels and antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase), and adenosine triphosphate content with histological, alkaline comet assay, and TEM examination of the hepatic tissues. CNPs showed that size distribution (polydispersity index) 0.350 nm and the zeta potential measurement of CNPs were found to be -14.9 mV which revealed the high stability of CNPs. DG induced biochemical and cellular alterations in the hepatic tissues. CNPs and V synergistically afforded protection against hepatic injury and oxidative stress resulting from aging that was induced by DG. Consequently, CNPs were an effective agent in the drug delivery in the hepatic diseases medications and act as a carrier for V and thus make synergistic effect between CNPs and V that achieved the high antioxidant capacities. CNPs and V improved the hepatic enzymes, which act as anti-inflammatory and antigenotoxicity, and improved the antioxidant capacities in the hepatic tissues.

The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate.

Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV-treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV-treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV.

EFFECT OF INDOMETHACIN AND ITS COMPLEXES ON REPRODUCTIVE PERFORMANCE AND OXIDATIVE STRESS IN TESTIS AND STOMACH OF MALE ALBINO RATS WITH REFERENCE TO THEIR CHEMICAL CHARACTERIZATIONS.

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.