Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring

Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Motejaded, Fatemeh; Rafatpanah, Houshang; Zabihi, Hoda; Hosseini, Mahmoud; Bideskan, Alireza Ebrahimzadeh

doi:10.1016/j.etap.2014.01.014

Cited by 119 publications

(76 citation statements)

References 34 publications

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“…Behavioral alterations following prenatal ENM exposure were previously reported (Hougaard et al 2010); however, specific studies of neurofunction yielded inconsistent behavioral and cognitive results (Cui et al 2014; Jackson et al 2011; Mohammadipour et al 2014). Therefore, converging findings from this and other studies highlight the importance of optimal prenatal health for the proper development of the CNS and the behaviors this system modulates.…”

Section: Discussionmentioning

confidence: 95%

“…Initial studies provide evidence that exposure to xenobiotic material during gestation may affect the health of future generations (Hougaard et al 2015; Stapleton 2015; Blum et al, 2015); including neurological outcomes and susceptibilities in learning and memory of young adult male offspring (Yokota et al 2015). Due to inconsistencies between animal species, offspring age, xenobiotic materials, maternal exposure routes, and behavioral/cognitive testing, studies of neurofunction after exposures have yielded variable behavioral and cognitive impairment results (Cui et al 2014; Hougaard et al 2010; Jackson et al 2011; Mohammadipour et al 2014). Therefore, the aim of this investigation was to develop an experimental design to characterize the behavioral and cognitive abilities of adult rat offspring.…”

Section: Introductionmentioning

confidence: 99%

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Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition

Engler-Chiurazzi

Stapleton

Stalnaker

et al. 2016

Journal of Toxicology and Environmental Health, Part A

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It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole body nanoparticle inhalation facility, pregnant Sprague Dawley rats (gestational day 7) were exposed 4 days per week to either filtered air (control) or nanotitanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9±6.4 nm, 10.4±0.4 mg/m3, 5 hr/day) for 7.8±0.5 days of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9±0.5 μg. Subsequently, at 5 months of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition

Engler-Chiurazzi

Stapleton

Stalnaker

et al. 2016

Journal of Toxicology and Environmental Health, Part A

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“…These findings indicate that the developmental brain is vulnerable to TiO 2 NP exposure, especially during the lactation period. 46 In addition, Mohammadipour et al 47 observed reduced hippocampal cell proliferation and decreased spatial memory, inhibitory memory, and learning ability in rat offspring after the maternal administration of TiO 2 NPs during pregnancy. In that study, rats were exposed to 100 mg/kg body weight of TiO 2 NPs every day, which is equivalent to ~6,000 mg/60 kg of body weight for humans, far lower than the LD 50 (dose required to kill 50% of a population of test animals) of TiO 2 for rats (12,000 mg/kg body weight) per the 1969 guidelines of the World Health Organization (WHO).…”

mentioning

confidence: 99%

Central nervous system toxicity of metallic nanoparticles

Feng¹,

Chen²,

Zhang³

et al. 2015

IJN

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Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed.

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“…The recent findings of severe neurological damage in neonatal mice pups after high-dose exposure to titanium oxide nanoparticles throughout pregnancy are representative of such studies [41]. The following sections examine the available data on placental uptake, passage and toxicity for the major classes of nanomaterials commonly explored for drug delivery.…”

Section: Safety and Biodistribution Of Manufactured Nanomaterials In Prmentioning

confidence: 96%

Therapeutic and Safety Considerations of Nanoparticle-Mediated Drug Delivery in Pregnancy

Keelan

Leong

et al. 2015

Nanomedicine (Lond.)

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Advances in nanotechnology have resulted in the design of effective, safe and tissue-selective nanocarriers for delivering therapeutics to treat malignancies, infections and other diseases. In pregnancy, nanoparticle-based drug formulations could have the potential to selectively target either the placenta and/or fetus, enabling 'fetal-friendly' drugs to be administered in pregnancy with minimal risk of off-target effects. A considerable amount of research has been carried out on maternal-placental-fetal nanoparticle uptake, transfer and toxicity using rodent and ex vivo models. However, the development of placental targeting strategies and the therapeutic evaluation of nanoformulations in pregnancy remains in its infancy. While some promising avenues are currently under investigation, much work is needed to bring the advantages of nanoparticle-based drug therapy in pregnancy to clinical reality.

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Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring

Cited by 119 publications

References 34 publications

Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition

Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition

Central nervous system toxicity of metallic nanoparticles

Therapeutic and Safety Considerations of Nanoparticle-Mediated Drug Delivery in Pregnancy

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