Esculetin and Fucoidan Attenuate Autophagy and Apoptosis Induced by Zinc Oxide Nanoparticles through Modulating Reactive Astrocyte and Proinflammatory Cytokines in the Rat Brain

Abstract

We examined the protective effects of esculetin and fucoidan against the neurotoxicity of ZnO NPs in rats. Ninety rats were divided into nine groups and pre-treated with esculetin or fucoidan 1 h before ZnO NP administration on a daily basis for 2 weeks. Serum and brain homogenates were examined by enzyme-linked immunosorbent assay (ELISA), and neurons, microglia, and astrocytes in the hippocampal region were examined with immunohistochemical analysis. The serum levels of interleukin-1-beta (IL-1β), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were altered in the ZnO NP treatment groups. Brain IL-1β and TNF-α levels were elevated after ZnO NP administration, and these effects were inhibited by esculetin and fucoidan. SOD, 8-OHdG, and acetylcholinesterase (AChE) levels in the brain were decreased after ZnO NP administration. The brain levels of beclin-1 and caspase-3 were elevated after ZnO NP treatment, and these effects were significantly ameliorated by esculetin and fucoidan. The number of reactive astrocytes measured by counting glial fibrillary acidic protein (GFAP)-positive cells, but not microglia, increased following ZnO NP treatment, and esculetin and fucoidan ameliorated the changes. Esculetin and fucoidan may be beneficial for preventing ZnO NP-mediated autophagy and apoptosis by the modulation of reactive astrocyte and proinflammatory cytokines in the rat brain.

Micelle encapsulation zinc‐doped copper oxide nanocomposites reverse Olaparib resistance in ovarian cancer by disrupting homologous recombination repair

“…It is well known that the HR pathway plays an important role in the development of ovarian cancer, and a defect in its function would potentially lead to a greater susceptible of tumor cells to drugs that are damaging to the cellular genome, including PARP inhibitors 14 . Over the years, many metal oxide NPs have been reported to exhibit anticancer activity by inducing autophagy 41–43 . In most cases, elevated cellular autophagy after nanoparticles treatment leads to increased cell death.…”

“… 14 Over the years, many metal oxide NPs have been reported to exhibit anticancer activity by inducing autophagy. 41 , 42 , 43 In most cases, elevated cellular autophagy after nanoparticles treatment leads to increased cell death. Zn‐CuO NPs previously developed were shown to induce cellular autophagy in pancreatic cancer to inhibit cell growth exerting antitumor effects, 30 and our current study shows that MEnZn‐CuO NPs can similarly induce autophagy in ovarian cancer.…”

Esculetin unveiled: Decoding its anti‐tumor potential through molecular mechanisms—A comprehensive review

“…A quick and environmentally friendly method was used to successfully create the nanocomposites of titanium dioxide nanoparticles adorned poly (diallyldimethylammonium chloride)‐functionalized grapheme (TiO2‐PDDA‐Gr) that optimize the efficiency of esculetin 94 . The purpose of the study performed by Song et al was to examine the protective effects of esculetin against neurotoxicity brought on by intragastric administration of zinc oxide nanoparticles (ZnO NPs) in Sprague–Dawley (SD) rats, which showed positive results 95 . According to these results, esculetin may be integrated into solid, stable nanoparticles to enhance biological processes.…”

“…Lu et al stated that the electrochemical response of esculetin was significantly improved by the addition of CdSe NPs to PDDA‐G over a range from 1.0 × 10 −8 to 5.0 × 10 −5 mol L −1 with a detection limit of 4.0 × 10 −9 mol L −1 ( S / N = 3) 91 . Administration of esculetin with zinc oxide nanoparticles elevated caspase‐3 expression 92 . When functionalized with the coumarin molecule, esculetin, amorphous calcium phosphate nanoparticles (ACP NPs) exhibit outstanding biocompatibility, and biodegradability features 93 .…”

“… 91 Administration of esculetin with zinc oxide nanoparticles elevated caspase‐3 expression. 92 When functionalized with the coumarin molecule, esculetin, amorphous calcium phosphate nanoparticles (ACP NPs) exhibit outstanding biocompatibility, and biodegradability features. 93 ACP NPs demonstrated a more focused cytotoxicity against colorectal cancer (CRC) cells (T‐84 cells) with an IC50 of 71.42 g/mL despite not harming human blood cells.…”