Quercetin and Idebenone Ameliorate Oxidative Stress, Inflammation, DNA damage, and Apoptosis Induced by Titanium Dioxide Nanoparticles in Rat Liver

Abstract

Titanium dioxide nanoparticles (TiO2-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 TiO2-NPs were evaluated in the current study. The results showed that the coadministration of Qur or Id to rats intoxicated with TiO2-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 TiO2-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 TiO2-NPs toxicity. The histopathological examination of the liver section showed that TiO2-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 TiO2-NPs and other hepatotoxic drugs.

Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms

“…The current study used idebenone at a dose of 200 mg/kg that previously ameliorated oxidative stress, pro-inflammatory cytokines and DNA damage in a titanium-dioxide-induced hepatotoxicity model [41], and also improved cardiac function [42]. Since administration of idebenone with food is known to increase its bioavailability by 5 to 7 times [43], idebenone was administered with chow pellets in the present study.…”

Quercetin mitigates liver injury in a rat model of liver cholestasis

“…Quercetin (3,3,4,5,7-pentahydroxyflavone), a natural flavonoid compound found in vegetables and fruits, has a prominent antioxidant, and anti-inflammatory activities [10]. Quercetin was found to downregulate the serum levels of immunoinflammatory mediators, TNF-α, IL-6 and Creactive protein, protecting liver in atitanium dioxide nanoparticles induced liver injury rat model [11]. Additionally, quercetin affords antifibrotic effect by preventing TGF-β signaling pathways and fibroblast activation in carbon tetrachloride and thioacetamide induced hepatic toxicity in rats [6].…”

Composition and Genoprotective Effect of the Flavonoidal Content of Lepidium sativum L. Methanolic Seed Extract against Cyclophosphamide- Induced DNA Damage in Mice

“…35 Further biochemical studies suggested that DNA protective role of quercetin was based on enhancement of antioxidant defense system reduced glutathione (GSH) level, catalase (CAT) and glutathione peroxidase (GPx) activities with reduction in oxidative stress parameters such as thiobarbituric acidreacting substance (TBARS), by deoperoxides and NO levels. 36,37 Kaempferol was shown to exhibit moderate antimutagenic effect. Glycosilation at C-3 showed no significant influence on glycosylated flavonoid antimutagenic activity.…”