Neurobehavioral and Ultrastructural Changes Induced by Phytosynthesized Silver-Nanoparticle Toxicity in an In Vivo Rat Model

Abstract

(1) Background: The study aimed to assess neurobehavioral, ultrastructural, and biochemical changes induced by silver nanoparticles synthesized with Cornus mas L. extract (AgNPs-CM) in rat brains. (2) Methods: The study included 36 male adult rats divided into three groups. Over a period of 45 days, AgNPs-CM (0.8 and 1.5 mg/kg b.w.) were administered daily by gavage to two of the groups, while the control group received the vehicle used for AgNP. After treatment, OFT and EPM tests were conducted in order to assess neurobehavioral changes. Six of the animals from each group were sacrificed immediately after completion of treatment, while the remaining six were allowed to recuperate for an additional 15 days. Transmission electron microscopy (TEM), GFAP immunohistochemistry, and evaluation of TNFα, IL-6, MDA, and CAT activity were performed on the frontal cortex and hippocampus. (3) Results: Treated animals displayed a dose- and time-dependent increase in anxiety-like behavior and severe ultrastructural changes in neurons, astrocytes, and capillaries in both brain regions. Immunohistochemistry displayed astrogliosis with altered cell morphology. TNFα, IL-6, MDA, and CAT activity were significantly altered, depending on brain region and time post exposure. (4) Conclusions: AgNPs-CM induced neurobehavioral changes and severe cell lesions that continued to escalate after cessation of exposure.

A Historical Review of Brain Drug Delivery

“…The silver content of brain increased 14-fold and 22-fold following the feeding of 30 nm and 10 nm AgNPs, respectively, which was associated with increased gene expression of inflammatory cytokines and impaired cognition [944]. Similar findings were made in rats fed AgNPs [945]. Silver ions may gain access to brain from blood similar to mechanisms that mediate the brain uptake of copper ions.…”

“…The greatest toxicity is observed with the chronic administration of either metallic NPs or CNTs/fullerenes. With respect to metallic NPs, toxicity is found after the administration of AuNPs [941][942][943], AgNPs [944,945], iron NPs [946], silica NPs [947], and titanium NPs [948]. Pregnant mice were fed AgNPs orally from the first to last day of gestation [944].…”

Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids

“…The effects of this impairment were shown to be deficits of memory acquisition and maintenance of long-term memory [24]. Other authors also observed steroid-related behavioral disorders, including anxiety-like behavior in mice exposed to citrate-coated AgNPs [45].…”

“…Similar results were also shown by Attia et al [44], who also found reduced TAS levels in mice exposed to high doses of citrate-coated AgNPs. In addition, recently, Opris et al [45] also found increased lipid peroxidation products and simultaneous severe ultrastructural changes in neurons and astrocytes in the hippocampus in rats orally exposed to AgNPs phytosynthesized with Cornus mas L. extract. This is in line with the results of our study, which also found elevated TBARS levels, but only in animals that received BSAcoated AgNPs.…”

“…On the other hand, AgNPs induce dysfunction of the mitochondria. The major mitochondrial ultrastructural changes noticed in animals treated with AgNPs suggested mitochondrial dysfunction as a response to stress conditions, consisting of swelling, altered cristae, and elongation [34,44,45]. Reported changes in mitochondrial functions are probably resulting from the interactions of Ag + ions with the thiol groups present in the inner mitochondrial membrane [53][54][55].…”