Fadda Laila M, Hagar Hanan, Mohamed Azza M, Ali Hanaa M
Faculty of Pharmacy, Pharmacology Department, King Saud University, Saudi Arabia.
Medical College and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
Dose Response. 2018 Dec 9;16(4):1559325818812188. doi: 10.1177/1559325818812188. eCollection 2018 Oct-Dec.
Titanium dioxide nanoparticles (TiO-NPs) are extensively used in a wide range of applications; however, many reports have investigated their nanotoxicological effect at the molecular level either in vitro or in vivo systems. The defensive roles of quercetin (Qur) or idebenone (Id) against the hepatotoxicity induced by TiO-NPs were evaluated in the current study. The results showed that the coadministration of Qur or Id to rats intoxicated with TiO-NPs markedly ameliorated the elevation in hepatic malondialdehyde (MDA), serum alanine amino-transferase (ALT), glucose, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), immunoglobin G (IgG), and C-reactive protein (CRP) levels compared to their levels in TiO-NPs-treated rats. The aforementioned antioxidants also effectively modulated the changes in the levels of serum vascular endothelial growth factor (VEGF), nitric oxide (NO), hepatic DNA breakage, caspase-3, and inhibition of drug metabolizing enzymes (cytochrome P450s; CYP4502E12E1) in rat livers induced by TiO-NPs toxicity. The histopathological examination of the liver section showed that TiO-NPs caused severe degeneration of most hepatocytes with an increase in collagen in the portal region, while treatment with the antioxidants in question improved liver architecture. These outcomes supported the use of Qur and Id as protective agents against the hepatotoxicity induced by TiO-NPs and other hepatotoxic drugs.
二氧化钛纳米颗粒（TiO-NPs）被广泛应用于众多领域；然而，许多报告已在体外或体内系统中研究了它们在分子水平上的纳米毒理学效应。在本研究中评估了槲皮素（Qur）或艾地苯醌（Id）对TiO-NPs诱导的肝毒性的防御作用。结果表明，与TiO-NPs处理的大鼠相比，将Qur或Id与TiO-NPs中毒的大鼠共同给药可显著改善肝丙二醛（MDA）、血清丙氨酸转氨酶（ALT）、葡萄糖、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、免疫球蛋白G（IgG）和C反应蛋白（CRP）水平的升高。上述抗氧化剂还有效调节了TiO-NPs毒性诱导的大鼠肝脏中血清血管内皮生长因子（VEGF）、一氧化氮（NO）、肝DNA断裂、半胱天冬酶-3水平的变化以及药物代谢酶（细胞色素P450s；CYP4502E12E1）的抑制。肝脏切片的组织病理学检查表明，TiO-NPs导致大多数肝细胞严重变性，门管区胶原蛋白增加，而用上述抗氧化剂治疗可改善肝脏结构。这些结果支持将Qur和Id用作对抗TiO-NPs和其他肝毒性药物诱导的肝毒性的保护剂。
