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The renal effects of a single and low dose of titanium dioxide nanoparticles in adult male rats
S190
Abstracts / Toxicology Letters 229S (2014) S40–S252
P-3.131 The renal effects of a single and low dose of titanium dioxide nanoparticles in adult male rats Carlos Enrique Escarcega-Gonzalez ∗ , Maria Luisa Rodriguez-Vazquez, Fernando Jaramillo-Juarez, Eduardo De La Cerda-Gonzalez, Haydee Martinez Ruvalcaba Francisco Anibal Posadas Del Rio Universidad Autonoma De Aguascalientes, Aguascalientes, Mexico The earliest and significant (p < 0.05) renal effects of a single and intravenous dose (5 mg/kg) of titanium dioxide (TiO2 ) nanoparticles to male and adult Wistar rats were: (a) increase of the enzymatic activity of ␥-glutamiltranspeptidase by 10 ± 1.7-fold, 15 ± 2.2-fold, 10 ± 0.1-fold, and 14 ± 1.0-fold, respectively, at 0–5 h, 5–24 h, 24–48 h, and 48–72 h. (b) Increase of the enzymatic activity of dipeptidylaminopeptidase IV (2.3 ± 0.2-fold, 4.2 ± 0.2-fold, 2.8 ± 0.2-fold, and 2.8 ± 0.1-fold, respectively), at all times tested. (c) Increase of the urine osmolarity 1.4 ± 0.07-fold, 1.9 ± 0.06-fold, 1.4 ± 0.1-fold, and 1.4 ± 0.02-fold, also at all times tested. (d) TiO2 also increased the concentration of urinary glucose, at later times (5–24 h, 24–48 h, and 48–72 h): 13.9 ± 1.5-fold, 7.5 ± 2.4-fold, and 10 ± 1.8-fold, respectively. (d) At the same times, TiO2 increased the concentration of urinary sodium by 1.4 ± 0.07-fold, 2.4 ± 0.5fold, 3.3 ± 0.3-fold, and 3.6 ± 0.2-fold, respectively. All these results were significantly different when compared with control rats. Thus, intravenous administration of a single and low dose of titanium dioxide nanoparticles produced enzymuria and hyperosmolarity as the earliest renal effects, in adult male rats. http://dx.doi.org/10.1016/j.toxlet.2014.06.644 P-3.132 Analysis of the preventive effect of Ginkgo biloba on renal effects of titanium dioxide nanoparticles in adult male rats Carlos Enrique Escarcega-Gonzalez 1,∗ , Maria Luisa Rodriguez-Vazquez 1 , Fernando Jaramillo-Juarez 1 , Eduardo De La Cerda-Gonzalez 1 , Haydee Martinez-Ruvalcaba 1 , Francisco Anibal Posadas Del Rio 1 , Bruno Alfonso Escalante-Acosta 2 1 Universidad Autonoma De Aguascalientes, Aguascalientes/Aguascalientes, Mexico, 2 Cinvestav, Monterrey/Nuevo Leon, Mexico
as the urine concentration of glucose and sodium, in most of the time periods, compared with control rats. The pretreatment with GbE reversed, near completely, all the renal effects of titanium dioxide. Thus, the GbE showed renoprotective effects against TiO2 probably due to stabilization of the cytoplasmic membrane and its antioxidant properties. http://dx.doi.org/10.1016/j.toxlet.2014.06.645 P-3.133 Toxic effects induced by poly(amidoamine) dendrimers in Allium cepa Paloma Fernández Freire 1,∗ , José Manuel Pérez Martín 1 , Ana Peropadre 1 , Mónica Aquilino 1 , Roberto Rosal 2 , María José Hazen 1 1 2
Universidad Autónoma Madrid, Madrid, Madrid, Spain, Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, Spain
Poly(amidoamine) (PAMAM) dendrimers are hyper-branched polymeric, nanoscale molecules with exceptional properties. They are globular, symmetric, have a large number of surface endgroups, and possess a remarkable core encapsulation ability, being excellent drug carriers for biomedical and pharmaceutical applications. They are also readily internalized in cells, a circumstance that have raised new concerns regarding their potential cytotoxicity to humans and the environment, considering that they will be eventually released becoming environmental pollutants. The toxicological properties of dendrimers have been mainly studied in human cell lines, but little is known about their potential ecotoxicological effects, apart from some studies in bacteria and freshwater algae. In this study, the effects of G2, G3 and G4 generation amineand hydroxyl-terminated PAMAM dendrimers were evaluated in Allium cepa onion bulbs. Root growth and mitotic index (MI) scoring were assayed for PAMAM dendrimers of generation G2, G3 and G4 with both terminations. Surprisingly, the results obtained in this first set of experiments did not show a clear relationship between the generation level and their toxicity, as it is generally accepted. Among them, dendrimers with EC50 values for root growth and MI (G2OH, G3OH and G3NH2) were selected to perform further studies. The evaluation of abnormalities during mitosis distinctively revealed a genotoxic effect, with features characteristic of chromosome stickiness, micronucleus formation and missegregation during anatelophase. These results suggest a potential environmental risk of PAMAM dendrimers and provide relevant data to define the toxicological profile of this kind of nanomaterials. http://dx.doi.org/10.1016/j.toxlet.2014.06.646
Nanotechnology is used to develop nanomaterials as vectors to drugs applied to treatment of several diseases. The effects of low doses of nanoparticles (NPs) on kidneys have not been well studied. Moreover, the commercial Ginkgo biloba extract (GbE) contains mainly flavonoids that are good antioxidants. The purpose of this work was to investigate the possible profilactic benefits of GbE on some renal effects of titanium dioxide (TiO2 ). We used Wistar rats (250 ± 20 g, body weight), divided in three groups (n = 6, each): A, administration of a single dose of TiO2 (5 mg/kg, b. w.) by the intravenous route; B administration of a single dose of GbE (10 mg/kg, b. w.) by the intraperitoneal route; and C, administration of a single dose of GbE (10 mg/kg, b. w., i.p.), 24 h before the administration of a single dose of TiO2 (5 mg/kg, b. w., i.v.). Rats were kept in metabolic cages and the urine was collected from 0 to 5, 5 to 24, 24 to 48 and 48 to 72 h, after last treatment. TiO2 increased the enzymatic activity, in urine, of two brush-border enzymes (␥-glutamyl transpepdidase and dipeptidilaminopeptidase-IV), the urinary osmolarity, as well
P-3.134 New biomarker: Novel, relevant, rapid, sensitive non-invasive electrophysiology technique and the potential role of P-glycoprotein in modulating silver nanoparticle toxicity in earthworms and aquatic oligochaetes Ravi Gooneratne ∗ , Noémie Demizieux, Martin Wellby Lincoln University, Lincoln, Canterbury, New Zealand An electrophysiological technique was used to compare the ecotoxicity of silver (Ag) nanoparticles (NPs) with that of silver nitrate (AgNO3 ) by measuring conduction velocity (CV) in the medial giant fibres (MGF) of earthworms and worms. Based on the LC10 and LC50 values, AgNP was 2- to 3-fold more toxic than AgNO3 and this was
Abstracts / Toxicology Letters 229S (2014) S40–S252
P-3.131 The renal effects of a single and low dose of titanium dioxide nanoparticles in adult male rats Carlos Enrique Escarcega-Gonzalez ∗ , Maria Luisa Rodriguez-Vazquez, Fernando Jaramillo-Juarez, Eduardo De La Cerda-Gonzalez, Haydee Martinez Ruvalcaba Francisco Anibal Posadas Del Rio Universidad Autonoma De Aguascalientes, Aguascalientes, Mexico The earliest and significant (p < 0.05) renal effects of a single and intravenous dose (5 mg/kg) of titanium dioxide (TiO2 ) nanoparticles to male and adult Wistar rats were: (a) increase of the enzymatic activity of ␥-glutamiltranspeptidase by 10 ± 1.7-fold, 15 ± 2.2-fold, 10 ± 0.1-fold, and 14 ± 1.0-fold, respectively, at 0–5 h, 5–24 h, 24–48 h, and 48–72 h. (b) Increase of the enzymatic activity of dipeptidylaminopeptidase IV (2.3 ± 0.2-fold, 4.2 ± 0.2-fold, 2.8 ± 0.2-fold, and 2.8 ± 0.1-fold, respectively), at all times tested. (c) Increase of the urine osmolarity 1.4 ± 0.07-fold, 1.9 ± 0.06-fold, 1.4 ± 0.1-fold, and 1.4 ± 0.02-fold, also at all times tested. (d) TiO2 also increased the concentration of urinary glucose, at later times (5–24 h, 24–48 h, and 48–72 h): 13.9 ± 1.5-fold, 7.5 ± 2.4-fold, and 10 ± 1.8-fold, respectively. (d) At the same times, TiO2 increased the concentration of urinary sodium by 1.4 ± 0.07-fold, 2.4 ± 0.5fold, 3.3 ± 0.3-fold, and 3.6 ± 0.2-fold, respectively. All these results were significantly different when compared with control rats. Thus, intravenous administration of a single and low dose of titanium dioxide nanoparticles produced enzymuria and hyperosmolarity as the earliest renal effects, in adult male rats. http://dx.doi.org/10.1016/j.toxlet.2014.06.644 P-3.132 Analysis of the preventive effect of Ginkgo biloba on renal effects of titanium dioxide nanoparticles in adult male rats Carlos Enrique Escarcega-Gonzalez 1,∗ , Maria Luisa Rodriguez-Vazquez 1 , Fernando Jaramillo-Juarez 1 , Eduardo De La Cerda-Gonzalez 1 , Haydee Martinez-Ruvalcaba 1 , Francisco Anibal Posadas Del Rio 1 , Bruno Alfonso Escalante-Acosta 2 1 Universidad Autonoma De Aguascalientes, Aguascalientes/Aguascalientes, Mexico, 2 Cinvestav, Monterrey/Nuevo Leon, Mexico
as the urine concentration of glucose and sodium, in most of the time periods, compared with control rats. The pretreatment with GbE reversed, near completely, all the renal effects of titanium dioxide. Thus, the GbE showed renoprotective effects against TiO2 probably due to stabilization of the cytoplasmic membrane and its antioxidant properties. http://dx.doi.org/10.1016/j.toxlet.2014.06.645 P-3.133 Toxic effects induced by poly(amidoamine) dendrimers in Allium cepa Paloma Fernández Freire 1,∗ , José Manuel Pérez Martín 1 , Ana Peropadre 1 , Mónica Aquilino 1 , Roberto Rosal 2 , María José Hazen 1 1 2
Universidad Autónoma Madrid, Madrid, Madrid, Spain, Universidad de Alcalá de Henares, Alcalá de Henares, Madrid, Spain
Poly(amidoamine) (PAMAM) dendrimers are hyper-branched polymeric, nanoscale molecules with exceptional properties. They are globular, symmetric, have a large number of surface endgroups, and possess a remarkable core encapsulation ability, being excellent drug carriers for biomedical and pharmaceutical applications. They are also readily internalized in cells, a circumstance that have raised new concerns regarding their potential cytotoxicity to humans and the environment, considering that they will be eventually released becoming environmental pollutants. The toxicological properties of dendrimers have been mainly studied in human cell lines, but little is known about their potential ecotoxicological effects, apart from some studies in bacteria and freshwater algae. In this study, the effects of G2, G3 and G4 generation amineand hydroxyl-terminated PAMAM dendrimers were evaluated in Allium cepa onion bulbs. Root growth and mitotic index (MI) scoring were assayed for PAMAM dendrimers of generation G2, G3 and G4 with both terminations. Surprisingly, the results obtained in this first set of experiments did not show a clear relationship between the generation level and their toxicity, as it is generally accepted. Among them, dendrimers with EC50 values for root growth and MI (G2OH, G3OH and G3NH2) were selected to perform further studies. The evaluation of abnormalities during mitosis distinctively revealed a genotoxic effect, with features characteristic of chromosome stickiness, micronucleus formation and missegregation during anatelophase. These results suggest a potential environmental risk of PAMAM dendrimers and provide relevant data to define the toxicological profile of this kind of nanomaterials. http://dx.doi.org/10.1016/j.toxlet.2014.06.646
Nanotechnology is used to develop nanomaterials as vectors to drugs applied to treatment of several diseases. The effects of low doses of nanoparticles (NPs) on kidneys have not been well studied. Moreover, the commercial Ginkgo biloba extract (GbE) contains mainly flavonoids that are good antioxidants. The purpose of this work was to investigate the possible profilactic benefits of GbE on some renal effects of titanium dioxide (TiO2 ). We used Wistar rats (250 ± 20 g, body weight), divided in three groups (n = 6, each): A, administration of a single dose of TiO2 (5 mg/kg, b. w.) by the intravenous route; B administration of a single dose of GbE (10 mg/kg, b. w.) by the intraperitoneal route; and C, administration of a single dose of GbE (10 mg/kg, b. w., i.p.), 24 h before the administration of a single dose of TiO2 (5 mg/kg, b. w., i.v.). Rats were kept in metabolic cages and the urine was collected from 0 to 5, 5 to 24, 24 to 48 and 48 to 72 h, after last treatment. TiO2 increased the enzymatic activity, in urine, of two brush-border enzymes (␥-glutamyl transpepdidase and dipeptidilaminopeptidase-IV), the urinary osmolarity, as well
P-3.134 New biomarker: Novel, relevant, rapid, sensitive non-invasive electrophysiology technique and the potential role of P-glycoprotein in modulating silver nanoparticle toxicity in earthworms and aquatic oligochaetes Ravi Gooneratne ∗ , Noémie Demizieux, Martin Wellby Lincoln University, Lincoln, Canterbury, New Zealand An electrophysiological technique was used to compare the ecotoxicity of silver (Ag) nanoparticles (NPs) with that of silver nitrate (AgNO3 ) by measuring conduction velocity (CV) in the medial giant fibres (MGF) of earthworms and worms. Based on the LC10 and LC50 values, AgNP was 2- to 3-fold more toxic than AgNO3 and this was