title: Beneficial effects of quercetin on oxidative stress in liver and kidney induced by titanium dioxide (TiO2) nanoparticles in rats.
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.
authors.affiliation: Doctorado en Farmacología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG) , Guadalajara, Jalisco , México .
authors.forename: Aarón Emmanuel
authors.initials: AE
authors.lastname: González-Esquivel
authors.forename: Claudia Lisset
authors.initials: CL
authors.lastname: Charles-Niño
authors.forename: Fermín Paul
authors.initials: FP
authors.lastname: Pacheco-Moisés
authors.forename: Genaro Gabriel
authors.initials: GG
authors.lastname: Ortiz
authors.forename: Fernando
authors.initials: F
authors.lastname: Jaramillo-Juárez
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Rincón-Sánchez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016503:Drug Delivery Systems; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; C009495:titanium dioxide; D011794:Quercetin; D014025:Titanium; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione
keywords: Kidney; liver; nanoparticles; oxidative stress; quercetin; rat; titanium dioxide (TiO2)