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槲皮素对雄性大鼠口服亚慢性同时暴露于氧化铝纳米粒子和醋酸铅所致肝毒性的改善作用。

Ameliorative effects of quercetin against hepatic toxicity of oral sub-chronic co-exposure to aluminum oxide nanoparticles and lead-acetate in male rats.

机构信息

Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2023 Apr;396(4):737-747. doi: 10.1007/s00210-022-02351-y. Epub 2022 Dec 6.

Abstract

The present study was designed to evaluate the probable ameliorative role of quercetin (QCN) against oxidative hepatotoxicity induced by aluminum oxide nanoparticles (AlONPs) with a diameter < 30 nm and lead acetate (Pb) co-exposure in adult male Sprague-Dawley rats. Rats were weighed and allocated to seven groups (n = 10 each) and were treated orally via orogastric gavage for 60 successive days: rats of the 1st group were kept as control given distilled water (1 ml/kg), rats of the 2nd group received 2 ml/kg BW/day corn oil; rats of the 3rd group were administered 20 mg/kg BW QCN/day; rats of the 4th group received 100 mg/kg BW AlONPs; rats of the 5th group received 50 mg/kg BW Pb; rats of the 6th group co-received AlONPs and Pb at the same previous doses; and rats of the 7th group were co-administered AlONPs, Pb, and QCN at the same previous doses. At the end of the experiment, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total, direct, indirect bilirubin, triglycerides, total cholesterol, HDL, VLDL, and LDL were estimated. The hepatic oxidative stress biomarkers as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx), were also evaluated. Finally, the histopathological and histomorphometric evaluations and the residues of Al and Pb in hepatic tissues were assessed. AlONPs and/or Pb exposure significantly elevated lipid peroxidation levels and considerably altered the hepatic biochemical parameters; nevertheless, QCN significantly reduced hepatic enzymes compared to toxicant exposed groups. Additionally, QCN significantly improved AlONPs-afforded liver tissue damage, as established in microscopic findings on the liver in the group treated with AlONPs + Pb. Conclusively, QCN could be a candidate natural agent to safeguard the liver versus the co-harmful impacts of AlONPs and Pb toxicity.

摘要

本研究旨在评估槲皮素(QCN)对直径<30nm 的氧化铝纳米粒子(AlONPs)和醋酸铅(Pb)共同暴露诱导的成年雄性 Sprague-Dawley 大鼠氧化肝毒性的可能改善作用。大鼠称重并分配到七组(每组 10 只),通过口服灌胃连续 60 天给药:第 1 组大鼠作为对照给予蒸馏水(1ml/kg),第 2 组大鼠给予 2ml/kg BW/天玉米油;第 3 组大鼠给予 20mg/kg BW QCN/天;第 4 组大鼠给予 100mg/kg BW AlONPs;第 5 组大鼠给予 50mg/kg BW Pb;第 6 组大鼠同时给予相同剂量的 AlONPs 和 Pb;第 7 组大鼠同时给予 AlONPs、Pb 和 QCN。实验结束时,测定血清碱性磷酸酶(ALP)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素、直接胆红素、间接胆红素、甘油三酯、总胆固醇、高密度脂蛋白(HDL)、极低密度脂蛋白(VLDL)和低密度脂蛋白(LDL)水平。还评估了肝氧化应激生物标志物超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GPx)。最后,评估了肝组织的组织病理学和组织形态学评价以及 Al 和 Pb 的残留量。AlONPs 和/或 Pb 暴露显著增加了脂质过氧化水平,并显著改变了肝生化参数;然而,与暴露于毒剂的组相比,QCN 显著降低了肝酶。此外,QCN 显著改善了 AlONPs 引起的肝组织损伤,这在 AlONPs+Pb 治疗组的肝组织显微镜检查结果中得到证实。总之,QCN 可能是一种天然候选药物,可防止肝脏受到 AlONPs 和 Pb 毒性的共同有害影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dcd/10042903/3d85be89648c/210_2022_2351_Fig1_HTML.jpg

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