Injected nanoparticles: The combination of experimental systems to assess cardiovascular adverse effects

Vlasova, Maria; Tarasova, O. S.; Riikonen, Joakim; Raula, Janne; Lobach, A. S.; Борзых, А. А.; Smirin, Boris V.; Kauppinen, Esko I.; Елецкий, А. В.; Herzig, Karl‐Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa‐Pekka; Järvinen, Kristiina

doi:10.1016/j.ejpb.2014.02.001

Cited by 21 publications

(13 citation statements)

References 22 publications

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“…The particles investigated in the current study, were much smaller in size, 12.0 and 15.0 nm compared to those tested by Vlasova et al ., suggesting this drop in MAP is not solely dependent on the size of the particles. The decrease in MAP following both doses of MNPs (0.5 and 2.0 mg/kg) in pigs, is smaller than those observed following 5.0 and 10.0 mg/kg in rats and mice, respectively …”

Section: Discussionsupporting

confidence: 88%

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Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig

Edge

Shortt

Gobbo

et al. 2016

Clin Exp Pharma Physio

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Manufactured nanomaterials have a variety of medical applications, including diagnosis and targeted treatment of cancer. A series of experiments were conducted to determine the pharmacokinetic, biodistribution and biocompatibility of two novel magnetic nanoparticles (MNPs) in the anaesthetized pig. Dimercaptosuccinic acid (DMSA) coated superparamagnetic iron oxide nanoparticles (MF66-labelled 12 nm, core nominal diameter and OD15 15 nm); at 0.5, or 2.0 mg/kg) were injected intravenously. Particles induced a dose-dependent decrease in blood pressure following administration which recovered to control levels several minutes after injection. Blood samples were collected for a 5-h period and stored for determination of particle concentration using particle electron paramagnetic resonance (pEPR). Organs were harvested post-mortem for magnetic resonance imaging (MRI at 1.5 T field strength) and histology. OD15 (2.0 mg/kg) MNP had a plasma half-life of approximately 15 min. Both doses of the MF66 (0.5 and 2.0 mg/kg) MNP were below detection limits. MNP accumulation was observed primarily in the liver and spleen with MRI scans which was confirmed by histology. MRI also showed that both MNPs were present in the lungs. The results show that further modifications may be required to improve the biocompatibility of these particles for use as diagnostic and therapeutic agents.

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Section: Discussionsupporting

confidence: 88%

“…Vlasova et al . proposed the decrease in MAP was due to both endothelium‐dependent and independent arterial vasodilation.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig

Edge

Shortt

Gobbo

et al. 2016

Clin Exp Pharma Physio

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“…Heart rate increases in mammals exposed to SWCNTs, silicon, or polymeric ENMs via intravenous injection (Vlasova et al, 2014) and similar responses are observed in isolated hearts exposed to nTiO 2 or silica ENMs (Stampfl et al, 2011). With the observed increase in multiple cellular stress markers, we expected a similar response in nZnO-treated fish here but instead, f h decreased by $35% after 10-15 h of exposure.…”

Section: Cardiorespiratory Responsessupporting

confidence: 78%

Cardiorespiratory toxicity of environmentally relevant zinc oxide nanoparticles in the freshwater fishCatostomus commersonii

Bessemer¹,

Butler²,

Tunnah³

et al. 2014

Nanotoxicology

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The inhalation of zinc oxide engineered nanomaterials (ENMs) has been linked to cardiorespiratory dysfunction in mammalian models but the effects of aquatic ENM exposure on fish have not been fully investigated. Nano-zinc oxide (nZnO) is widely used in consumer products such as sunscreens and can make its way into aquatic ecosystems from domestic and commercial wastewater. This study examined the impact of an environmentally relevant nZnO formulation on cardiorespiratory function and energy metabolism in the white sucker (Catostomus commersonii), a freshwater teleost fish. Evidence of oxidative and cellular stress was present in gill tissue, including increases in malondialdehyde levels, heat shock protein (HSP) expression, and caspase 3/7 activity. Gill Na(+)/K(+)-ATPase activity was also higher by approximately three-fold in nZnO-treated fish, likely in response to increased epithelial permeability or structural remodeling. Despite evidence of toxicity in gill, plasma cortisol and lactate levels did not change in animals exposed to 1.0 mg L(-1) nZnO. White suckers also exhibited a 35% decrease in heart rate during nZnO exposure, with no significant changes in resting oxygen consumption or tissue energy stores. Our results suggest that tissue damage or cellular stress resulting from nZnO exposure activates gill neuroepithelial cells, triggering a whole-animal hypoxic response. An increase in parasympathetic nervous signaling will decrease heart rate and may reduce energy demand, even in the face of an environmental toxicant. We have shown that acute exposure to nZnO is toxic to white suckers and that ENMs have the potential to negatively impact cardiorespiratory function in adult fish.

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“…Recently, telemetry systems have been adopted to assess the potential effects of therapeutics, including that of SPIONs, aluminum and thermally hydro‐carbonized porous silicon NPs on the CVS (Iversen et al ., ; Vlasova et al ., ,b). These studies provided an insight into the application of telemetry as a suitable approach for long‐term CVS studies.…”

Section: Overview Of the Currently Available Nano‐sized Construct‐relmentioning

confidence: 99%

Preclinical safety assessments of nano‐sized constructs on cardiovascular system toxicity: A case for telemetry

Cheah

Kiew

Lee

et al. 2017

J of Applied Toxicology

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While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS.

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Injected nanoparticles: The combination of experimental systems to assess cardiovascular adverse effects

Cited by 21 publications

References 22 publications

Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig

Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig

Cardiorespiratory toxicity of environmentally relevant zinc oxide nanoparticles in the freshwater fishCatostomus commersonii

Preclinical safety assessments of nano‐sized constructs on cardiovascular system toxicity: A case for telemetry

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