ABSTRACT
New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 µM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.
ABSTRACT
The wide application of nanotechnology merits the need to clarify their nanotoxicity. In vivo studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2 NPs), but there are limited data on chromosomal abnormalities induced in hepatic tissue. In this article, the toxicity of three IP doses of TiO2 NPs (80 nm) (50, 250, and 500 mg/kg) through three time intervals (up to 7, 15, and 45 days) on liver tissue was assessed. Hepatic catalase (CAT), glutathione (GSH), nitric oxide (NOx), and malondialdehyde (MDA) levels varied with the administered dose and exposure time of TiO2 NPs. As a result, TiO2 NPs caused a statistically significant decrease in hepatic CAT and GSH activities and a significant alleviation in MDA and NOx levels (p < 0.05), suggesting that the liver exposed to these various doses of TiO2 NPs suffered from severe oxidative stress. The extent of depletion of antioxidant enzymes and the elevation of MDA and NOx in the liver exposed to the highest dose and duration of TiO2 NPs 500 mg for 45 days was the greatest, suggesting that the toxicity might be dose and time dependent. Further, C-reactive protein (CRP) as an inflammatory marker was also alleviated, in addition to the apparent chromosomal aberration and liver pathologies including necrotic and fibrotic hepatocytes after exposure to 250 and 500 mg/kg of TiO2 NPs for 14 and 45 days that were deduced. Hence, nanotechnology-based industries are growing rapidly leading to large-scale production of engineered nanoparticles. They contribute to increased chances of human NPs exposure and health risk.
