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Safe Administration of Carbon Nanotubes by Intravenous Pathway in BALB/c Mice.

ABSTRACT: Carbon nanotubes (CNTs) are nanomaterials with multiple possible uses as drug carriers or in nanovaccine development. However, the toxicity of CNTs administered intravenously in in vivo models has not been fully described to date. This work aimed to evaluate the toxic effect of pristine multi-walled CNTs (UP-CNTs), purified (P-CNTs), or CNTs functionalized with fluorescein isothiocyanate (FITC-CNTs) administered by intravenous injection in BALB/c mice. Biochemical and histopathological parameters were analyzed at 1, 14, 29, and 60 days post-exposure. Pristine CNTs were the most toxic nanoparticles in comparison with P-CNTs or FITC-CNTs, increasing serum AST (? 180%), ALT (? 300%), and LDH (? 200%) levels at one day post-exposure. The urea/creatinine ratio suggested pre-renal injury at the 14th day accompanied of extensive lesions in kidneys, lungs, and liver. Biochemical and histological findings in mice exposed to P-CNTs had not significant differences compared to the controls. A lower toxic effect was detected in animals exposed to FITC-CNTs which was attributable to FITC toxicity. These results demonstrate that the purification process of CNTs reduces in vivo toxicity, and that toxicity in functionalized CNTs is dependent on the functionalized compound. Therefore, P-CNTs are postulated as potential candidates for safe biomedical applications using an intravenous pathway.

SUBMITTER: Guzman-Mendoza J

PROVIDER: S-EPMC7075304 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Safe Administration of Carbon Nanotubes by Intravenous Pathway in BALB/c Mice.

Guzmán-Mendoza Jesús J Montes-Fonseca Silvia Lorena SL Ramos-Martínez Ernesto E González-Horta Carmen C Hernández-Rodríguez Pilar Del Carmen PDC Orrantia-Borunda Erasmo E Chávez-Flores David D Sánchez-Ramírez Blanca B

Nanomaterials (Basel, Switzerland) 20200224 2

Carbon nanotubes (CNTs) are nanomaterials with multiple possible uses as drug carriers or in nanovaccine development. However, the toxicity of CNTs administered intravenously in <i>in vivo</i> models has not been fully described to date. This work aimed to evaluate the toxic effect of pristine multi-walled CNTs (UP-CNTs), purified (P-CNTs), or CNTs functionalized with fluorescein isothiocyanate (FITC-CNTs) administered by intravenous injection in BALB/c mice. Biochemical and histopathological pa ...[more]

PMID: 32102423

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Project description:BackgroundCurrently, medical treatment of inflammatory pain is limited by a lack of safe and effective therapies. Triptonide (TPN), a major component of Tripterygium wilfordii Hook.f. with low toxicity, has been shown to have good anti-inflammatory and neuroprotective effects. The present study aims to investigate the effects of TPN on chronic inflammatory pain.Materials and methodsInflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA). TPN's three different doses were intravenously administered to compare the analgesic efficacy: 0.1 mg/kg, 0.5 mg/kg, and 2.0 mg/kg. The foot swelling was quantitated by measuring paw volume. Mechanical allodynia and thermal hyperalgesia were assessed with von Frey filament testing and Hargreaves' test, respectively. Western blots, qRT-PCR and immunofluorescence tests were used to analyze the expression of pAKT, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Two AKT inhibitors, AKT inhibitor Ⅳ and MK-2206, were used to examine AKT's effects on pain behavior and cytokines expression.ResultsIntravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons. However, these effects were suppressed by treatment with TPN. Furthermore, TPN treatment inhibited CFA-induced increase of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Consistent with the in vivo data, TPN inhibited LPS-induced Akt phosphorylation and inflammatory mediator production in ND7/23 cells. Finally, intrathecal treatment with AKT inhibitor Ⅳ or MK-2206, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and simultaneously decreased the mRNA expression of TNF-α, IL-1β, and IL-6 in DRG.ConclusionThese data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.

Dataset Information

Safe Administration of Carbon Nanotubes by Intravenous Pathway in BALB/c Mice.

Publications

Safe Administration of Carbon Nanotubes by Intravenous Pathway in BALB/c Mice.

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