Beneficial effects of quercetin on oxidative stress in liver and kidney induced by titanium dioxide (TiO2) nanoparticles in rats

Toxicol Mech Methods. 2015 Mar;25(3):166-75. doi: 10.3109/15376516.2015.1006491. Epub 2015 Feb 11.

Abstract

TiO2 nanoparticles used as vectors for the delivery of drugs have shown greater effectiveness. However, TiO2 nanoparticles can cause oxidative stress in liver and kidney, so we analyzed if a previous or simultaneous quercetin treatment could counteract this in rats. Five groups of male Wistar rats (200-250 g) were included: (1) healthy controls, (2) TiO2 group, (3) quercetin group, (4) preventive group: quercetin for 5 days prior to exposure of TiO2, and (5) therapeutic group: TiO2 (5 mg/kg, i.v.) plus quercetin single dose for 5 days (5 mg/kg/day, i.p.). Hepatic and renal function tests were made. Five animals from each group were sacrificed (0, 14 and 28 days), and liver and kidney tissue were obtained. Malondialdehyde (MDA), reduced/oxidized glutathione, and activity of glutathione peroxidase/reductase were measured, as well as the level of gene expression by q-PCR. There were no significant changes in serum ALT and AST activities. More damage was observed at 14 versus 28 days, because TiO2 was excreted in urine. Quercetin indeed showed a renal protective effect by increasing glutathione reductase and peroxidase levels and reducing MDA levels. On the other hand, TiO2 liver damage was less pronounced with quercetin as therapeutic treatment. TiO2 induces significantly the glutathione reductase expression and it can be down-regulated by quercetin. Biochemical tests in serum and urine showed a better effect of quercetin administered in the therapeutic group. Care should be taken with the dose and time of administration of quercetin, because this antioxidant could also have a pro-oxidant effect.

Keywords: Kidney; liver; nanoparticles; oxidative stress; quercetin; rat; titanium dioxide (TiO2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Drug Delivery Systems
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glutathione / agonists
  • Glutathione / antagonists & inhibitors
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Glutathione Peroxidase / antagonists & inhibitors
  • Glutathione Peroxidase / chemistry
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / antagonists & inhibitors
  • Glutathione Reductase / chemistry
  • Glutathione Reductase / genetics
  • Glutathione Reductase / metabolism
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / physiopathology
  • Male
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / toxicity*
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Quercetin / administration & dosage
  • Quercetin / therapeutic use*
  • Random Allocation
  • Rats, Wistar
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / drug therapy
  • Renal Insufficiency / physiopathology
  • Renal Insufficiency / prevention & control
  • Titanium / administration & dosage
  • Titanium / toxicity*

Substances

  • Antioxidants
  • titanium dioxide
  • Quercetin
  • Titanium
  • Glutathione Peroxidase
  • Glutathione Reductase
  • Glutathione