Silver Nanoparticles In Rats Research Articles

Evaluation of the Safety and Efficacy of Curcumin-Synthesized Silver Nanoparticles in Rats Exposed to Chlorpyrifos During Puberty Development.

Silver nanoparticles (Ag-NPs) have garnered significant attention in recent years due to their therapeutic effects. Curcumin (CUR) has been utilized as a coating agent for synthesizing Ag-NPs, intended to act as a potential drug. This study was designed to evaluate the safety and efficacy of curcuminsynthesized silver nanoparticles on rats exposed to chlorpyrifos (CPF) during their pubertal development. Forty-two male Wistar rats, 23 days old, were selected and randomly divided into 7 groups (n=6) as follows: positive control, negative control, CPF (5 mg/kg), silver nanoparticles synthesized using curcumin at 40 μg/kg (CUR-Ag-NPs 40), CUR-Ag-NPs 80, CPF+ CUR-Ag-NPs 40, CPF+ CUR-AgNPs 80. All treatments were administered via gavage for 30 days. At the end of the study, rats were anesthetized using ketamine (50 mg/kg), and xylazine, (10 mg/kg) and blood was collected from the heart for serum analysis of liver enzymes, urea, and creatinine. Liver and kidney tissues were isolated for histopathological analysis. No significant differences were observed in serum levels of AST, ALT, and ALP enzymes as well as urea and creatinine levels among the different groups. Light microscopy observation revealed multifocal inflammatory mononuclear cell subsets in liver tissue associated with mild inflammatory mononuclear cell infiltration in the portal region in CPF, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40, and CPF+CUR-Ag- NPs 80 groups. Histological examination of kidney tissue showed degenerative changes in the tubular epithelium, congestion, and mild infiltration of mononuclear inflammatory cells in the renal interstitial tissue in the CPF group, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40 and CPF+CUR-Ag-NPs 80 groups. This study failed to establish the safety and efficacy of CUR-Ag-NP at 40 and 80 μg/kg in prepubertal rats exposed to CPF. However, further studies should be conducted to thoroughly characterize the efficacy of CUR-Ag-NP in developmental animal models.

Tissue Distribution, Pharmacokinetics, and Effect of Hematological and Biochemical Parameters of Acute Intravenous Administration of Silver Nanoparticles in Rats.

The widespread biomedical and commercial applications of silver nanoparticles (AgNPs) have increased their potential for human and environmental exposure and toxicity to human health. The bio-distribution and toxicity of AgNPs in rodents following inhalation, intratracheal instillation, and oral ingestion are well documented; however, little is known about the bio-distribution of intravenously (IV)-administered AgNPs and their organ-specific pathophysiological effects. Here, we investigate the pharmacokinetic pattern and tissue distribution of AgNPs in male rats following IV administration. The animals were humanely sacrificed after 10 min, 1 h, 6 h, 12 h, 24 h, and 168 h of AgNP administration, and the silver (Ag) content was measured from blood samples and various tissues following acid digestion. The AgNPs were readily absorbed and subsequently distributed into most organs predominantly in the colon, small intestine, kidney, and heart after 6 h; however, they were the highest in the spinal cord after 168 h. White blood cells (WBCs) were significantly increased (42-60%) in AgNP-administered animals at all time points except 10 min. Regarding platelets, all AgNP-administered animals showed counts 7.8-39.2% lower, with the lowest count at 168 h post-administration. In the case of lymphocytes (LYMs), the AgNP-treated animals exhibited a count 19.5-41% lower at 10 min and 1 h post-administration; however, the animals at 168 h post-administration showed a count 30.5% more. The mean corpuscular hemoglobin (MCH) counts from the AgNP-treated animals were decreased by 50-62%. The concentrations of aspartate transaminase (AST), urea, and creatinine were increased in the AgNP-treated animals. Taken together, the results suggest that the acute IV administration of AgNPs alters metabolic and hematological parameters in animals and may pose a health risk to humans.

The potential curative role of Avena sativa extract against oxidative stress, DNA damage and apoptosis induced by acute hepatotoxicity of silver nanoparticles in rats.

Silver nanoparticles (Ag NPs or nanosilver) have pulled in expanding interest because of their novel physical, substance, and organic properties contrasted with their full scale scaled partners. The goal of this study was to investigate if Avena sativa (AVS) extract could ameliorate Ag NPs toxicity-induced alterations in liver structure and function, DNA damage, apoptosis, and oxidative stress. Twenty adult male rats were assigned randomly to four groups: control, AVS (intragastrically, 5g/Kg body weight/day) for 2 weeks, Ag NPs (400 mg/kg body weight/day) for 1 week as acute toxicity and Ag NPs + AVS (same therapy of Ag NPs as acute toxicity with AVS). This study demonstrated a statistical significant increase in serum levels of liver function tests (AST, ALT, ALP and globulin), liver DNA damage, apoptotic P53 and Malondialdehyde after Ag NPs administration when compared to control group. Conversely, statistical significant decreases were detected in serum albumin, total proteins, liver reduced glutathione, catalase, superoxide dismutase, glutathione S-transferase and anti-apoptotic Bcl2 in Ag NPs group as compared to control group. Interestingly, treatment of Ag NPs with AVS (Ag Nps + AVS) was associated with significant improvements of the studied parameters, liver structure and functions. Avena sativa (AVS) extract could scavenge free radicals producing beneficial effects against acute Ag NPs hepatotoxicity in rats induced through activation of oxidative stress and apoptosis.

Biochemical, molecular and cytological impacts of alpha-lipoic acid and Ginkgo biloba in ameliorating testicular dysfunctions induced by silver nanoparticles in rats.

Silver nanoparticles (AgNPs) are commonly utilized in medicine. However, they have negative effects on the majority of organs, including the reproductive system. AgNPs were reported to be able to reach the testicular tissues due to their nano size, which allows them to pass through blood-testicular barriers. The goal of this study was to see if alpha-lipoic acid (LA) or Ginkgo biloba (GB) might protect adult rat testes after intraperitoneal injection of AgNPs. Forty male healthy adult Wister albino rats were randomly assigned to four groups: control, AgNPs-intoxicated group intraperitoneally injected AgNPs 50mg/kg b.w, 3 times a week; LA + AgNPs group intoxicated with AgNPs and orally gavaged with 100mg LA/kg b.w; and GB + AgNPs group injected with AgNPs and orally given GB extract 120mg/kg b.w for 30 consecutive days. Biochemical changes (testosterone, ACP, and prostatic acid phosphatase), oxidative indices, mRNA expression of proapoptotic (BAX) and anti-apoptotic (BCL-2) biomarkers, histological, and immunohistochemical changes in testicular tissues were investigated. Significant decrease in serum testosterone level and elevation in ACP and PACP enzyme activity in AgNPs-treated rats. As well, there were lowering in tGSH, GSH GR, GPx, and elevation in MDA and GSSG values. AgNPs-exposed rats expressed downregulation of testicular thirodexin-1 (Txn-1), transforming growth factor-1β (TGF-1β), anti-apoptotic (BCL-2), and upregulaion of proapoptotic biomarkers (BAX) mRNA expressions. Strong positive action to BAX and lowering the action of Ki-67 antibody were observed. Because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with LA or GB could be beneficial in reducing the harmful effects of AgNPs on the testicles.

Neurotherapeutic effects of prodigiosin conjugated with silver-nanoparticles in rats exposed to cadmium chloride-induced neurotoxicity

Prodigiosin is a red pigment produced by Serratia marcescens strain. Bacterial prodigiosin and its synthetic derivatives are efficacious antioxidants and proapoptotic agents. This study illustrates a new approach for use of prodigiosin conjugated silver nanoparticles (PG-AgNP2) against cadmium chloride (CdCl2) induced neurotoxicity in rats. Rats were (ip) injected with Cd (6.5 mg/kg) for 7 days with or without PG-AgNP2 (3 mg/kg). The concentration of Cd, DA, NE, 5-HT, amino acids, NO, MDA, SOD, GSH, catalase, TNF-α, IL-6, Bax, Bcl2 and Caspase-3. The Cd-intoxicated group showed a significant increase in Cd concentration in brain tissue, in addition, to an increase in MDA and NO and a decrease in the content of neurotransmitters (DA, NE, and 5-HT), inhibitory amino acids, and level of all studied antioxidant enzymes. PG-AgNP2 treatment, significantly reduced Cd-induced brain tissue injury as indicated by increased antioxidant molecules, neurotransmitters (DA, NE, and 5-HT), and inhibitory amino acids accompanied by lower oxidative stress indices (MDA and NO) and excitatory amino acids in brain tissue. PG-AgNP2 decreased inflammatory mediators including pro-inflammatory cytokines and prevented the development of apoptosis in the brain tissue. Our findings suggest that PG-AgNP2 can act as a therapeutic agent against neuronal impairments associated with Cd exposure.

Kinetic time courses of inhaled silver nanoparticles in rats.

Silver nanoparticles (Ag NPs) are priority substances closely monitored by health and safety agencies. Despite their extensive use, some aspects of their toxicokinetics remain to be documented, in particular following inhalation, the predominant route of exposure in the workplace. A same experimental protocol and exposure conditions were reproduced two times (experiments E1 and E2) to document the kinetic time courses of inhaled Ag NPs. Rats were exposed nose-only to 20nm Ag NPs during 6h at a target concentration of 15mg/m3 (E1: 218,341 ± 85,512 particles/cm3; E2, 154,099 ± 5728 particles/cm3). The generated aerosol showed a uniform size distribution of nanoparticle agglomerates with a geometric mean diameter ± SD of 79.1 ± 1.88nm in E1 and 92.47 ± 2.19nm in E2. The time courses of elemental silver in the lungs, blood, tissues and excreta were determined over 14days following the onset of inhalation. Excretion profiles revealed that feces were the dominant excretion route and represented on average (± SD) 5.1 ± 3.4% (E1) and 3.3 ± 2.5% (E2) of the total inhaled exposure dose. The pulmonary kinetic profile was similar in E1 and E2; the highest percentages of the inhaled dose were observed between the end of the 6-h inhalation up to 6-h following the end of exposure, and reached 1.9 ± 1.2% in E1 and 2.5 ± 1.6% in E2. Ag elements found in the GIT followed the trend observed in lungs, with a peak observed at the end of the 6-h inhalation exposure and representing 6.4 ± 4.9% of inhaled dose, confirming a certain ingestion of Ag NPs from the upper respiratory tract. Analysis of the temporal profile of Ag elements in the liver showed two distinct patterns: (i) progressive increase in values with peak at the end of the 6-h inhalation period followed by a progressive decrease; (ii) second increase in values starting at 72h post-exposure with maximum levels at 168-h followed by a progressive decrease. The temporal profiles of Ag elements in lymphatic nodes, olfactory bulbs, kidneys and spleen also followed a pattern similar to that of the liver. However, concentrations in blood and extrapulmonary organs were much lower than lung concentrations. Overall, results show that only a small percentage of the inhaled dose reached the lungs-most of the dose likely remained in the upper respiratory tract. The kinetic time courses in the gastrointestinal tract and liver showed that part of the inhaled Ag NPs was ingested; lung, blood and extrapulmonary organ profiles also suggest that a small fraction of inhaled Ag NPs progressively reached the systemic circulation by a direct translocation from the respiratory tract.

Subacute toxicity of decahedron and spheral silver nanoparticles in rats

The safety of nanomaterials and nanotechnologies is an important factor in the regulation of industrial production and the introduction of nanoproducts into practice. The toxicological aspect of the use of silver nanoparticles (SNP) is insufficiently studied, leaving many questions without answer. The problem of dependence of toxicity on the shape and the size of nanoparticles is controversial and not well-studied, and there is a lack of research on the nanosilver effect on human and animal organisms. Objective. The aim of the work was to provide the hygienic assessment of harmful effects of silver nanoparticles of spherical and decahedron shape. Materials and Methods. Samples of solutions of spherical and decahedron SNP, synthesized by the method of photostimulated restoration, were intraperitoneally administered to white nonlinear rats both males and females aged 4 months. For the subacute toxicity study of spherical 45-nm nanosilver the animals were subdivided into three groups of (16 rats in each, 8 animals in a subgroup — according to gender). Every day they were injected with spherical SNP at doses of 0.1,1 and 5 mg/kg intraperitoneally for 14 days. The fourth group was the biological control. For the subacute toxicity study of decahedron 45-nm nanosilver the animals were subdivided into four groups (16 rats in each, 8 animals in the subgroup according to gender). The animals were injected intraperitoneally with 10, 5,1, and 0.1 mg/kg doses of SNP daily for 14 days. Fifth group was biological control. On 14th day animals were withdrawn from the experiment by decapitation under a slight, ethereal athetic. Results and Discussion. It was grounded the expediency of taking into account the physical and chemical properties of silver nanoparticles, including geometrical characteristics (shape, specific area of surface), the number of silver ions in nanoparticle and the quantity of nanoparticles in the solution while the determination of exposition of nanosilver or other nanochemicals of different geometric shapes. On models of subacute effect there were determined the peculiarities of different shapes nanosilver exposure and hygienic meaning of biochemical and pathomorphological changes as criteria of harmful effect. With the help of morphometric analysis of pathomorphological changes of internal organs of rats there was ascertained doserelated harmful effect of decahedron and spherical silver nanoparticles. As a result of the experiment, dose-dependent circulating swelling of the epithelium of convoluted tubules of the kidneys, hepatocytes, nuclei of cardiomyocytes, alteration of the epithelium of bronchi of different caliber, repletion of the blood vessels of the walls of the respiratory parts of the lungs, karyopicnosis of neurons of the cerebral cortex were observed. The revealed changes in the indices of prooxidant-antioxidant equilibrium, some biochemical indices and the changes in internal organs of animals testified to the less toxic effect of silver nanospheres in comparison with silver nanodecahedrons. Conclusions. 1. According to the analysis of the geometric characteristics of decahedron silver nanoparticles, it is established that the specific area of decaheders is 2 times bigger than the specific area of the spherical SNP, which provides twice bigger area of the contact of silver nanodecahedron in the biological environment. The decahedron nanoparticle contains 4.3 times less atoms than spherical, and, at the same mass concentration, a solution of nanosilver contains 4 times more silver nano decahedrons than spheres. 2. With the help of biochemical analyses of blood and liver tissue, as well as the morphometric analysis of pathological changes in the internal organs of laboratory rats, the dose-dependent harmful effect of silver nanoparticles of decahedral and, partially, spherical shape was established. The revealed changes in the blood and internal organs of animals testified to a less toxic effect of silver nanospheres in comparison with silver nanodecahedrons. 3. It was established that the differences in biochemical and pathomorphological changes in the internal organs of laboratory animals at the same dose of SNP the decahedron and spherical shape, calculated in mg/kg body weight, are related to a 4-multiple dose difference expressed in the ratio of «the number of nanoparticles/kg» of body weight and a 9-multiple difference in favor of nanodecahedrons while calculating the dose «specific surface area/kg» of body weight. Key Words: silver nanoparticles, silver nanodecahedron, silver nanosphere, toxicity, nanosilver.

Toxicopathological and immunological studies on different concentrations of chitosan-coated silver nanoparticles in rats.

BackgroundMuch consideration has been paid to the toxicological assessment of nanoparticles prior to clinical and biological applications. While in vitro studies have been expanding continually, in vivo investigations of nanoparticles have not developed a cohesive structure. This study aimed to assess the acute toxicity of different concentrations of chitosan-coated silver nanoparticles (Ch-AgNPs) in main organs, including liver, kidneys, and spleen.Materials and methodsTwenty-eight male albino rats were used and divided into 4 groups (n=7). Group 1 was kept as a negative control group. Groups 2, 3, and 4 were treated intraperitoneally with Ch-AgNPs each day for 14 days at doses of 50, 25, and 10 mg/kg body weight (bwt) respectively. Histopathological, morphometric and immunohistochemical studies were performed as well as oxidative stress evaluations, and specific functional examinations for each organ were elucidated.ResultsIt was revealed that Ch-AgNPs induced dose-dependent toxicity, and the repeated dosing of rats with 50 mg/kg Ch-AgNPs induced severe toxicities. Histopathological examination showed congestion, hemorrhage, cellular degeneration, apoptosis and necrosis in hepatic and renal tissue as well as lymphocytic depletion with increasing tangible macrophages in the spleen. The highest levels of malondialdehyde, alanine aminotransferase, aspartate aminotransferase (MDA, ALT, AST) and the lowest levels of reduced glutathione, immunoglobulin G, M and total protein (GSH, IgG, IgM, TP) were observed in this group. On the other hand, repeated dosing with 25 mg/kg induced mild to moderate disturbance in the previous parameters, while there was no significant difference in results of pathological examination and biochemical tests between the control group and those treated with 10 mg/kg bwt Ch-AgNPs.ConclusionChitosan-coated silver nanoparticles induce dose-dependent adverse effects on rats.

Oral subchronic exposure to silver nanoparticles in rats

Because of their extremely small size, silver nanoparticles (AgNPs) show unique physical and chemical properties, with specific biological effects, which make them particularly attractive for being used in a number of consumer applications. However, these properties also influence the potential toxicity of AgNPs. In this study, we assessed the potential toxic effects of an in vivo oral sub-chronic exposure to polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) in adult male rats. We also assessed if oral PVP-AgNPs exposure could alter the levels of various metals (Fe, Mg, Zn and Cu) in tissues. Rats were orally given 0, 50, 100 and 200 mg/kg/day of PVP-AgNPs. Silver (Ag) accumulation in tissues, Ag excretion, biochemical and hematological parameters, metal levels, as well as histopathological changes and subcellular distribution following PVP-AgNPs exposure, were also investigated. After 90 days of treatment, AgNPs were found within hepatic and ileum cells. The major tissue concentration of Ag was found in ileum of treated animals. However, all tissues of PVP-AgNPs-exposed animals showed increased levels of Ag in comparison with those of rats in the control group. No harmful effects in liver and kidney, as well as in biochemical markers were noted at any treatment dose. In addition, no hematological or histopathological changes were found in treated animals. However, significant differences in Cu and Zn levels were found in thymus and brain of PVP-AgNPs-treated rats.

Hepatotoxicity and Nephrotoxicity of Repeated Oral Administration of Silver Nanoparticles in Rats

Hepatotoxicity and Nephrotoxicity of Repeated Oral Administration of Silver Nanoparticles in Rats

Toxicological effects of silver nanoparticles in rats

Toxicity of nanoparticles depends on chemical composition, atomic arrangement and particle size. Silver is being widely used in consumer medical products, due to its uniqueness such as antimicrobial activity. In this study, we assessed the toxic effects of size-silver nanoparticles 70 nanometer in rat’s living tissues, with different doses such as 0.25, 0.5, 1 and 2 mg/kg body weight on kidney, liver and spleen tissues via oral gavage for 30 days. Adverse impacts on liver, spleen and kidney were observed in a high dose-treated group (1 and 2 mg/kg), when determined by histopathological analysis.Pathological examination showed tissue damages, bloodshed, cell necrosis and apoptosis from all rat in high dose group compared to control group. Based on these results, it is suggested that the effect of nanosilver particles on the tissues may cause organ toxicity in rats. Key words: Silver, nanoparticle, kidney, liver, spleen, toxicity, rat.

Single and repeated oral dose toxicity studies of silver nanoparticles in rats

Single and repeated oral dose toxicity studies of silver nanoparticles in rats

Biodistribution and toxicity of silver nanoparticles in rats after subchronic oral administration

Biodistribution and toxicity of silver nanoparticles in rats after subchronic oral administration

Bioavailability and Toxicokinetics of citrate-coated silver nanoparticles in rats

Bioavailability, tissue distribution, blood concentration, and excretion of citrate-coated silver nanoparticles (AgNPs; size, 7.9 ± 0.95 nm by TEM diameter) were investigated. Male SD rats were treated by a single oral or intravenous administration of either 1 or 10 mg/kg AgNPs. Silver concentration of blood was determined at 10 min, and at 1, 2, 4, 8, 24, 48, and 96 h after treatment. Silver in the liver, lungs, and kidneys was also measured at 24 and 96 h after treatment. Excretion of silver nanoparticles via feces and urine was determined at 24 h after treatment. After oral administration, most AgNPs were found in feces, and their blood concentration was very low. This suggests that absorption through the gastrointestinal tract was not good. However, a high level of silver in the blood was detected after tail vein injection. When rats were injected with 1 mg/kg AgNPs, the silver concentration of blood was significantly elevated at 10 min after injection; the level subsequently decreased. In the rats treated with 10 mg/kg AgNPs, the elevated level did not decrease, but was maintained during the experimental period. On the basis of the values of AUC(oral)/AUC(iv), the bioavailability of orally administered AgNPs was 1.2% in the group treated with 1 mg/kg AgNPs and 4.2% in the group treated with 10 mg/kg AgNPs. AgNPs accumulated in the liver, lungs, and kidneys; the accumulated AgNPs were released into the blood stream. AgNP levels in the urine were extremely low compared to the levels in the feces. When rats were injected with AgNPs, these particles were also detected in feces at 24 h after treatment, which suggests bile secretion of AgNPs.

Distribution, Translocation and Accumulation of Silver Nanoparticles in Rats

Silver nanoparticles (SNPs) are widely used in the field of biomedicine, but a comprehensive understanding of how SNPs distribute in the body and the induced toxicity remains largely unknown. The present study was designed to investigate the distribution and accumulation of SNPs in rats with subcutaneous injection. Rats were injected with either SNPs or silver microparticles (SMPs) at 62.8 mg/kg, and then sacrificed at predetermined time points. The main organs of the experimental animals were harvested for ultrastructural analysis by transmission electron microscopy (TEM) and for silver content analysis by inductively coupled plasma mass spectrometry (ICP-MS). Results indicated that SNPs translocated to the blood circulation and distributed throughout the main organs, especially in the kidney, liver, spleen, brain and lung in the form of particles. SMPs, however, could not invade the blood stream, or organ tissues. Ultrastructural observations indicate that those SNPs that had accumulated in organs could enter different kinds of cells, such as renal tubular epithelial cells and hepatic cells. Moreover, SNPs also induced blood-brain barrier (BBB) destruction and astrocyte swelling, and caused neuronal degeneration. The results suggest more cautions needed in biomedical applications of SNPs, in particular, the long-term uses.