The Protective Roles of Vitamin E and α-Lipoic Acid Against Nephrotoxicity, Lipid Peroxidation, and Inflammatory Damage Induced by Gold Nanoparticles.

BACKGROUND: Recently, use of nanotechnology in biomedical applications such as drug delivery and diagnostic and therapeutic tools has increased greatly. This study evaluated gold nanoparticle (GNPs)-induced nephrotoxic effects in rats in vivo, and examined protective effects of alpha-lipoic acid (α-Lip) and Vitamin E (Vit E) against nephrotoxicity, lipid peroxidation, and inflammatory kidney damage induced by GNPs. MATERIALS AND METHODS: Twenty-four male Wistar-Kyoto rats (220-240 g, 12 weeks old) were dosed with 50 µL of 10 nm GNPs administered intraperitoneally with or without 200 mg/kg/day Vit E or 200 mg/kg/day α-Lip. Serum was prepared for biochemical analyses. Kidney function was evaluated through measurement of creatinine (CR), uric acid (URIC), and blood urea nitrogen (BUN). Oxidative stress and lipid peroxidation were evaluated by measurement of reduced glutathione (GSH) and malondialdehyde (MDA) in kidney tissue homogenates. RESULTS AND CONCLUSIONS: The results showed a significant rise in serum kidney function biomarkers including urea, URIC, CR, and BUN in GNP-treated rats compared to normal control rats. Furthermore, GNPs led to decreased GSH and elevated MDA levels. Vit E or α-Lip supplementation showed a beneficial effect against nephrotoxicity, lipid peroxidation, and inflammatory kidney damage induced by GNPs. This study suggests that use of natural antioxidants in combination with GNPs may be a useful tool in preventing GNPs toxicity.

Effects of quercetin and arginine on the nephrotoxicity and lipid peroxidation induced by gold nanoparticles in vivo.

INTRODUCTION: This study aimed to evaluate the nephrotoxicity caused by gold nanoparticles (GNPs) and investigate the potential roles of quercetin (Qur) and arginine (Arg) in mitigating the inflammatory kidney damage and dysfunction and inhibiting the toxicity induced by GNPs in rats. METHODS: Kidney function was assessed using various serum biomarkers, including blood urea nitrogen (BUN), uric acid (URIC), and creatinine (CR), while toxicity was evaluated by measuring the biomarkers glutathione (GSH) and malondialdehyde (MDA) in kidney tissues. RESULTS: Administration of GNPs to the rats severely affected the serum kidney biomarkers, as confirmed by the notable increases in BUN, URIC, and CR. Substantial changes in the levels of the biomarkers MDA and GSH in the kidney tissues were also observed, with a reduced level of GSH and elevated MDA activity. The administration of Qur or Arg exerted a protective effect against GNP-induced inflammatory kidney damage and toxicity, but with different responses according to their evaluated normalized values. CONCLUSION: This study demonstrates the beneficial effects of supplementation with Qur or Arg during the treatment with GNPs, potentially providing a powerful tool for cancer therapy.

Potential effects of different natural antioxidants on inflammatory damage and oxidative-mediated hepatotoxicity induced by gold nanoparticles.

OBJECTIVE: The objective of this study was to verify and confirm the oxidative-mediated hepatotoxicity, inflammatory liver damage, and oxidative stress induced by intraperitoneal administration of gold nanoparticles (GNPs) in vivo; characterize the effect of different natural antioxidants on these hazardous changes; and finally choose the most powerful antioxidant among these different natural antioxidants. METHODS: Ten-nanometer GNPs were dissolved in aqueous solution of 0.01% concentration. A dose of 50 µL of 10 nm GNPs was administered intraperitoneally for 7 days to the rats, whereas the antioxidants were orally administered for the same time period. The antioxidants used in the study were vitamin E (Vit E), α-lipoic acid (ALA), quercetin (Qur), arginine (Arg), and melanin. Forty Wistar-Kyoto male rats were used. Rats were arbitrarily divided into seven groups after acclimatization for 1 week. For serum separation, blood samples were obtained from each animal. Serum liver function markers and tissue oxidative stress and lipid proxidation biomarkers were assessed. RESULTS: The increase in the levels of gamma-glutamyl transferase, alkaline phosphatase, total protein, alanine aminotransferase, and total bilirubin in the serum of rats and the increase of malondialdehyde in the hepatic tissue and decrease in reduced glutathione when compared with the control in this study confirmed the ability of GNPs to cause hazardous effects. CONCLUSION: Treatment of rats with Vit E, ALA, Qur, Arg, and melanin along with GNPs significantly inhibited the inflammatory liver damage, lipid peroxidation, and the oxidative stress induced by GNPs in vivo, but with different responses due to their evaluated normalization values, and it has been confirmed that melanin is the most powerful antioxidant among these different natural antioxidants, ie, it has the most effective potential role against the hepatic inflammatory damage, oxidative stress, and lipid peroxidation.

Effect of melanin on gold nanoparticle-induced hepatotoxicity and lipid peroxidation in rats.

INTRODUCTION: Melanin pigments are produced by melanocytes and are believed to act as antioxidants based on the belief that melanin can suppress electronically stirred states and scavenge the free radicals. MATERIALS AND METHODS: The study was aimed to verify and prove the toxicity induced by administration of gold nanoparticles (GNPs) and to characterize the role of melanin as an antioxidant against inflammatory liver damage, oxidative stress, and lipid peroxidation induced intraperitoneally by GNPs in vivo. RESULTS: The findings from this study confirmed that administration of GNPs intraperitoneally caused liver damage in addition to producing oxidative stress and fatty acid peroxidation. The treatment of rats with melanin along with GNPs induced dramatic changes in all the measured biochemical parameters. Our data demonstrated that melanin completely inhibited inflammatory liver damage, oxidative stress, and lipid peroxidation, which was confirmed by the histological investigation of different liver sections stained by H&E. CONCLUSION: These results suggest the beneficial use of melanin together with GNPs for alleviating its toxicity. Other studies should be implemented taking into consideration the role of melanin in comparison with other natural antioxidants.

The protective role of quercetin and arginine on gold nanoparticles induced hepatotoxicity in rats.

BACKGROUND: The aim of the study was to confirm the hepatotoxicity induced by small-sized gold nanoparticles (GNPs) and evaluate the role of quercetin (Qur) and arginine (Arg) against hepatotoxicity caused by GNPs. METHODS: Twenty-five healthy male Wistar-Kyoto rats were used. GNPs were administered intraperitoneally to these rats at the dose of 50 µL for seven consecutive days. The role of Qur and Arg antioxidants against toxicity induced by GNPs was detected through the measurement of serum liver function and oxidative stress biomarkers in the liver tissues. RESULTS: Coadministration of Qur and Arg along with GNPs significantly induced dramatic alterations in the biochemical parameters. Levels of malondialdehyde, gamma-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, and total protein increased significantly in the GNPs injected group than in the control group, while reduced glutathione was greatly reduced in the GNPs group than in the control group. It also significantly decreased liver enzymes and the oxidative stress, therefore improving the liver damage and hepatotoxicity induced by GNPs. CONCLUSION: This study demonstrated that Qur and Arg antioxidants effectively improved the hepatic oxidative damage induced by GNPs. It also substantiates the application of Qur and Arg as protecting stand-in against GNPs' hepatotoxicity.

Pharmacological Properties of Melanin and its Function in Health.

The biological pigment melanin is present in most of the biological systems. It manifests a host of biological and pharmacological properties. Its role as a molecule with special properties and functions affecting general health, including photoprotective and immunological action, are well recognized. Its antioxidant, anti-inflammatory, immunomodulatory, radioprotective, hepatic, gastrointestinal and hypoglycaemic benefits have only recently been recognized and studied. It is also associated with certain disorders of the nervous system. In this MiniReview, we consider the steadily increasing literature on the bioavailability and functional activity of melanin. Published literature shows that melanin may play a number of possible pharmacological effects such as protective, stimulatory, diagnostic and curative roles in human health. In this MiniReview, possible health roles and pharmacological effects are considered.

The dosimetric properties of phosphate glass systems prepared by different chemical nanomaterials.

The synthesis and characterization of glass systems were carried out using prepared nanocrystals injected into a glass matrix as a thermoluminescence (TL) activator using the melt-quenching method. Sample 1 was prepared as [40P2 O5 50BaO:2.5MgO, 2.5Na2 O, 5TiO2 ], sample 2 as [37.5P2 O5 37.5CaO:25TiO2 ] and sample 3 as [50P2 O5 -50Li2 O]. Formation of the synthesized compound was confirmed by studying the X-ray diffraction (XRD) patterns and scanning electron microscopy (SEM) images. An annealing procedure was carried out for 1 h at 400 °C. The glow curve position and shape shifted dramatically and linearly to the higher temperature values on increasing the heating rate. A heating rate of 30 °C/s was the most suitable for obtaining a high TL response. Samples 2 and 3 have the highest TL response, which approached the effective atomic number (Zeff ) of natural bone. The observed TL sensitivity of the prepared samples 2 and 3 is less than that of commercially available 'TLD-200 chips' and LiF:Mg,Ti (TLD-100) phosphor. Sample [37.5P2 O5 37.5CaO:25TiO2 ] would be useful in personal and environmental dosimetry for measuring high doses of gamma radiation. Sample [50P2 O5 -50Li2 O] is a good dosimeter, although it requires the addition of an appropriate transitional metal (activator) to overcome the problem of high fading. Copyright © 2016 John Wiley & Sons, Ltd.

Short Communication: Rheological properties of blood serum of rats after irradiation with different gamma radiation doses in vivo.

The blood serum rheological properties open the door to find suitable radio-protectors and convenient therapy for many cases of radiation exposure. The present study aimed to investigate the rheological properties of rat blood serum at wide range of shear rates after whole body irradiation with different gamma radiation doses in vivo. Healthy male rats were divided into five groups; one control group and 4 irradiated groups. The irradiation process was carried out using Co60 source with dose rate of 0.883cG/sec. Several rheological parameters were measured using Brookfield LVDV-III Programmable rheometer. A significant increase in viscosity and shear stress was observed with 25 and 50Gy corresponding to each shear rate compared with the control; while a significant decrease observed with 75 and 100Gy. The viscosity exhibited a Non-Newtonian behaviour with the shear rate while shear stress values were linearly related with shear rate. The decrease in blood viscosity might be attributed to changes in molecular weight, pH sensitivity and protein structure. The changes in rheological properties of irradiated rats' blood serum might be attributed to destruction changes in the haematological and dimensional properties of rats' blood products.

Ultraviolet-visible and fluorescence spectroscopy techniques are important diagnostic tools during the progression of atherosclerosis: diet zinc supplementation retarded or delayed atherosclerosis.

BACKGROUND: In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. METHODS: The control rabbits group was fed on 100 g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470 ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. RESULTS: We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192 nm. In addition, they showed that supplementation of zinc (350 ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280 nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. CONCLUSIONS: This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis.

The gold nanoparticle size and exposure duration effect on the liver and kidney function of rats: In vivo.

UNLABELLED: Nanoparticles (NPs) offer a great possibility for biomedical application, not only to deliver pharmaceutics, but also to be used as novel diagnostic and therapeutic approaches. Currently, there are no data available regarding to what extent the degree of the toxicity and the accumulation of gold nanoparticles (GNPs) are present in in vivo administration. This study aimed to address the GNP size and exposure duration effect on the liver and kidney function of rats: in vivo. METHODS: A total of 30 healthy male Wistar-Kyoto rats of the same age (12 weeks old) and weighing 220-240 g of King Saud University colony were used. Animals were randomly divided into groups, two GNP-treated rat groups and one control group (CG). The 50 µl of 10 and 50 nm GNPs was intraperitoneally administered in rats for exposure duration of 3 days. Then, several biochemical parameters such as aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alanine transaminase (ALT), alkaline phosphatase (ALP), urea (UREA) and creatinine (CREA) were evaluated. RESULTS: In this study, the AST values increased with the administration of 10 and 50 nm GNPs compared with the control. The AST values significantly increased with 10 nm GNPs compared with 50 nm GNPs and control. The GGT and ALT values decreased with the administration of 10 and 50 nm GNPs compared with the control. The GGT and ALT values significantly decreased with 50 nm GNPs compared with 10 nm GNPs and control. The ALP values significantly decreased with the administration of 10 and 50 nm GNPs compared with the control. The decrease in ALP values with 10 nm GNPs was higher than those compared with 50 nm GNPs. In this study, the levels of UREA and CREA values increased in a non significant manner after the administration of 10 and 50 nm GNPs compared with the control. CONCLUSIONS: This study demonstrates that the increase in the enzymes AST and the decrease in ALP are smaller GNPs (10 nm) size-dependent for exposure duration of 3 days; while the decrease in the enzymes GGT and ALT are bigger GNPs (50 nm) size-dependent. The levels of UREA and CREA values indicated no significant changes with the administration of 10 and 50 nm GNPs for exposure duration of 3 days compared with the control. The administration of 10 and 50 nm GNPs for short exposure duration of 3 days induced only significant variations with some liver enzymes while kidney showed no significant variations. This study suggests that synthesis and metabolism of GNPs as well as the protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.

Uptake of gold nanoparticles in several rat organs after intraperitoneal administration in vivo: a fluorescence study.

BACKGROUND: The gold nanoparticles (GNPs) have potential applications in cancer diagnosis and therapy. In an attempt to characterise the potential toxicity or hazards of GNPs as a therapeutic or diagnostic tool, the fluorescence spectra in several rat organs in vivo were measured after intraperitoneal administration of GNPs. METHODS: The experimental rats were divided into control and six groups (G1A, G1B, G2A, G2B, G3A, and G3B; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion of GNPs for 3 days; B: infusion of GNPs for 7 days). The fluorescence measurements were investigated in the liver, kidney, heart, and lung organs of rats after intraperitoneal administration of GNPs for periods of 3 and 7 days in vivo. RESULTS: The 10 and 20 nm GNPs exhibited spherical morphology shape, while the 50 nm GNPs exhibited hexagonal shape. A sharp decrease in the fluorescence intensity induced with the larger 50 nm GNPs in the liver, kidney, heart, and lung organs of rats at the exposure duration of 3 and 7 days in vivo compared with the smaller 10 and 20 nm GNPs was observed. CONCLUSIONS: The decrease in fluorescence intensity may be attributed to occurrence of strong quenching, decrease in number and surface area of GNPs, and high clearance of GNPs via urine and bile. Moreover, decreasing size may lead to an exponential increase in surface area relative to volume, thus making GNPs surface more reactive on aggregation and to its surrounding biological components. The size, shape, surface area, number, and clearance of GNPs play a key role in toxicity and accumulation in the different rat organs. This study demonstrates that fluorescence peak intensity is particle size and exposure duration dependent. This study suggests that fluorescence intensity can be used as a useful tool for pointing to bioaccumulation and toxicity induced by GNPs in the different rat organs.

Effects of naked gold nanoparticles on proinflammatory cytokines mRNA expression in rat liver and kidney.

The data on the biocompatibility of naked gold nanoparticles (GNPs) are scarce, and their interpretation is controversial. We studied the acute (1 day) and subchronic (5 days) effects of GNPs (10 and 50 nm diameter) on expression of interleukin-1 beta (IL-1 ß ), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF- α ) in the liver and kidneys of rats. In the liver, the GNPs of both sizes (10 and 50 nm) significantly increased the cytokines gene expression on day 1 which was subsided on day 5; the GNPs of 50 nm size produced more severe inflammatory response as compared to smaller sized GNPs. In the kidney, the GNPs did not produce any significant change in the expression of IL-1 ß . Although the gene expression of IL-6 and TNF- α was not affected by GNPs of 10 nm size, 50 nm GNPs significantly increased the expression of IL-6 and TNF- α in the kidneys of rats on day 1 after treatment which returned to normalcy on day 5. These findings indicate the possible immunocompatibility of medium sized GNPs as they caused only a transient acute phase increase in proinflammatory cytokines expression followed by their normalcy during the repeated exposure.

Identification of potential biomarkers of gold nanoparticle toxicity in rat brains.

BACKGROUND: Gold nanoparticles (AuNPs) are finding increased use in therapeutics and imaging. However, their toxic effects still remain to be elucidated. Therefore this study was undertaken to study the biochemical effects of AuNPs on rat brain and identify potential biomarkers of AuNP toxicity. METHODS: Male Wister rats weighing 150-200 g were injected with 20 µg/kg body weight of 20-nm gold nanoparticles for 3 days through the intraperitoneal route. The rats were killed by carbon dioxide asphyxiation 24 h after the last dose of gold nanoparticle injection. The parameters studied included lipid peroxidation, glutathione peroxidase, 8- hydroxydeoxyguanosine, caspase-3, heat shock protein70, serotonin, dopamine, gamma amino-butyric acid and interferon-γ. RESULTS: In this study AuNPs caused generation of oxidative stress and a decrease of antioxidant enzyme, viz., glutathione peroxidase activity in rat brain. This was accompanied by an increase in 8-hydroxydeoxyguanosine, caspase-3 and heat shock protein70, which might lead to DNA damage and cell death. Gold nanoparticles also caused a significant decrease in the levels of neurotransmitters like dopamine and serotonin, indicating a possible change in the behavior of the treated animals. There was a significant increase in the cerebral levels of IFN-γ in treated animals. CONCLUSION: This study concludes that AuNPs cause generation of oxidative stress and an impairment of the antioxidant enzyme glutathione peroxidase in rat brain. AuNPs also cause generation of 8-hydroxydeoxyguanosine (8OHdG), caspase-3 and heat shock protein70 (Hsp70), and IFN-γ, which may lead to inflammation and DNA damage/cell death.

Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration.

BACKGROUND: Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs) on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. METHODS: To investigate particle-size effect of GNPs on the hepatic tissue, a total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days). RESULTS: In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltrate by chronic inflammatory cells and congestive dilated central veins. CONCLUSIONS: The induced histological alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These alterations were size-dependent with smaller ones induced the most effects and related with time exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and nuclear destruction may suggest that GNPs interact with proteins and enzymes of the hepatic tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS) generation which in turn may induce stress in the hepatocytes to undergo atrophy and necrosis. More histomorphologcal, histochemical and ultrastrucural investigations are needed in relation of the application of GNPs with their potential threat as a therapeutic and diagnostic tool.

The rheological properties of different GNPs.

BACKGROUND: Rheological analysis can be employed as a sensitive tool in predicting the physical properties of gold nanoparticles (GNPs). Understanding the rheological properties of GNPs can help to develop a better therapeutic cancer product, since these physical properties often link material formulation and processing stages with the ultimate end use. The rheological properties of GNPs have not been previously documented. The present study attempted to characterize the rheological properties of different sizes of GNPs at: 1) fixed temperature and wide range of shear rates; 2) varied temperature and fixed shear rate. METHODS: 10, 20 and 50 nm GNPs was used in this study. Several rheological parameters of GNPs such as viscosity, torque%, shear stress and shear rate were evaluated using Brookfield LVDV-III Programmable rheometer supplied with temperature bath and controlled by a computer. To measure fluid properties (viscosity as function of shear rate), e.g., to determine whether the flow is Newtonian or non-Newtonian flow behaviour, and viscoelasticity (viscosity as function of temperature), rheological parameters were firstly measured at starting temperature of 37°C and wide range of shear rates from 375 to 1875 s(-1), and secondly at a gradual increase of temperature from 37 to 42°C and fixed shear rate of 1875 s(-1). RESULTS: The 10, 20 and 50 nm GNPs showed mean size of 9.45 ± 1.33 nm, 20.18 ± 1.80 nm, and 50 nm GNPs, respectively. The 10 and 20 nm GNPs showed spherical morphology while 50 nm GNPs showed hexagonal morphology using the transmission electron microscope (TEM). The relation between viscosity (cp) and shear rate (s(-1)) for 10, 20 and 50 nm GNPs at a temperature of 37°C showed non-Newtonian behaviour. Although the relationship between SS (dyne/cm(2)) and SR (s(-1)) for 10, 20 and 50 nm GNPs was linearly related however their fluid properties showed non-Newtonian behaviour. CONCLUSIONS: The torque%, viscosity (cp) and SS (dyne/cm(2)) of all GNP sizes decreased with increasing the temperature and with decreasing the GNP size (for each fixed temperature value). For each shear rate value, the viscosity of all GNPs decreased with decreasing the GNP size. This study demonstrates that the physical, dimensional and morphological changes of GNPs have effective influence on their rheological properties. To understand and categorize the role of GNPs in drug delivery and cancer therapy, GNPs of varying size, number of particles, shape and surface should be taken into consideration. Moreover, further additional in vivo studies after administration of GNPs in rats should be performed to support this hypothesis.

Effect of gold nanoparticles on glutathione and malondialdehyde levels in liver, lung and heart of rats.

We studied the effect of gold nanoparticles (NPs) on oxidative stress markers including reduced glutathione (GSH) and malondialdehyde (MDA) in different organs of rats. Adult male Wistar-Kyoto rats were randomly divided into 3 groups of 5 animals each. One group served as control and received vehicle only. The remaining two groups were treated with 50 µl of 10 nm sized gold NPs, daily for 3 and 7 days, respectively. The rats were sacrificed 24 h after the last injection of NPs. Administration of gold NPs did not cause any significant change in GSH levels in liver, lung and heart on day 3 or day 7. There was no significant effect of gold NPs on MDA levels in lung and heart whereas significant increases in MDA levels were found in the liver of rats treated with gold nanoparticles on both 3 and 7 days post-dosing (ANOVA F = 7.113, P = 0.010). In conclusion, the findings of this preliminary study suggest that gold NPs of 10 nm diameter produce significant lipid peroxidation in rat liver however lungs and heart do not show any oxidative stress. Further studies are warranted to examine the effects of a broader dose range of gold NPs on the levels of free radical indices in different organs of rats.

Gold nanoparticles administration induces disarray of heart muscle, hemorrhagic, chronic inflammatory cells infiltrated by small lymphocytes, cytoplasmic vacuolization and congested and dilated blood vessels.

BACKGROUND: Despite significant research efforts on cancer therapy, diagnostics and imaging, many challenges remain unsolved. There are many unknown details regarding the interaction of nanoparticles (NPs) and biological systems. The structure and properties of gold nanoparticles (GNPs) make them useful for a wide array of biological applications. However, for the application of GNPs in therapy and drug delivery, knowledge regarding their bioaccumulation and associated local or systemic toxicity is necessary. Information on the biological fate of NPs, including distribution, accumulation, metabolism, and organ specific toxicity is still minimal. Studies specifically dealing with the toxicity of NPs are rare. The aim of the present study was to investigate the effects of intraperitoneal administration of GNPs on histological alterations of the heart tissue of rats in an attempt to identify and understand the toxicity and the potential role of GNPs as a therapeutic and diagnostic tool. METHODS: A total of 40 healthy male Wistar-Kyoto rats received 50 µl infusions of 10, 20 and 50 nm GNPs for 3 or 7 days. Animals were randomly divided into groups: 6 GNP-treated rats groups and one control group (NG). Groups 1, 2 and 3 received infusions of 50 µl GNPs of size 10 nm (3 or 7 days), 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively. RESULTS: In comparison with the respective control rats, exposure to GNPs doses produced heart muscle disarray with a few scattered chronic inflammatory cells infiltrated by small lymphocytes, foci of hemorrhage with extravasation of red blood cells, some scattered cytoplasmic vacuolization and congested and dilated blood vessels. None of the above alterations were observed in the heart muscle of any member of the control group. CONCLUSIONS: The alterations induced by intraperitoneal administration of GNPs were size-dependent, with smaller ones inducing greater affects, and were also related to the time exposure to GNPs. These alterations may indicate scattered cytoplasmic vacuolization, which may induce the toxicity effect through an inability to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. These histological alterations were more prominent with 10 nm size particles than with the larger ones. The interaction of GNPs with proteins and various cell types should be considered as part of the toxicological evaluation. Additional experiments related to plasma, tissues cytokine, antioxidant defense mechanism, lipid peroxidation, histomorphologcal and ultrastructure will be performed to identify and understand the toxicity and the potential use of GNPs as therapeutic and diagnostic tools.

Liver uptake of gold nanoparticles after intraperitoneal administration in vivo: a fluorescence study.

BACKGROUND: One particularly exciting field of research involves the use of gold nanoparticles (GNPs) in the detection and treatment of cancer cells in the liver. The detection and treatment of cancer is an area in which the light absorption and emission characteristics of GNPs have become useful. Currently, there are no data available regarding the fluorescence spectra or in vivo accumulation of nanoparticles (NPs) in rat liver after repeated administration. In an attempt to characterise the potential toxicity or hazards of GNPs in therapeutic or diagnostic use, the present study measured fluorescence spectra, bioaccumulation and toxic effects of GNPs at 3 and 7 days following intraperitoneal administration of a 50 µl/day dose of 10, 20 or 50 nm GNPs in rats. METHODS: The experimental rats were divided into one normal group (Ng) and six experimental groups (G1A, G1B, G2A, G2B, G3A and G3B; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion of GNPs for 3 days; B: infusion of GNPs for 7 days). A 50 µl dose of GNPs (0.1% Au by volume) was administered to the animals via intraperitoneal injection, and fluorescence measurements were used to identify the toxicity and tissue distribution of GNPs in vivo. Seventy healthy male Wistar-Kyoto rats were exposed to GNPs, and tissue distribution and toxicity were evaluated after 3 or 7 days of repeated exposure. RESULTS: After administration of 10 and 20 nm GNPs into the experimental rats, two fluorescence peaks were observed at 438 nm and 487 nm in the digested liver tissue. The fluorescence intensity for 10 and 20 nm GNPs (both first and second peaks) increased with the infusion time of GNPs in test rats compared to normal rats. The position of the first peak was similar for G1A, G2A, G1B, G2B, G3B and the normal (438 nm); that for G3A was shifted to a longer wavelength (444 nm) compared to the normal. The position of the second peak was similar for G1A, G1B, G2A, G2B and the control (487 nm), while it was shifted to a shorter wavelength for G3A (483 nm) and G3B (483 nm). The fluorescence intensity of the first and second peaks increased for G1A, G2A, G1B and G2B, while it decreased for G3A and G3B compared to the control. CONCLUSIONS: The fluorescence intensity of GNPs varied with the number, size and shape of particles and with the ratio of surface area to volume in a given sample. Fluorescence intensity changes during infusion depended on the size and shape of GNPs, with smaller particles experiencing larger changes during the infusion time in addition to the quenching produced by the larger GNPs. It is likely that smaller particles, which have a much higher ratio of surface area to volume compared to larger particles, are more prone to aggregation and surface interaction with biological components. This study suggests that fluorescence intensity can be used to evaluate bioaccumulation and the toxicity of gold nanoparticles in rats.

Exposure to gold nanoparticles produces cardiac tissue damage that depends on the size and duration of exposure.

BACKGROUND: Current research focuses on cancer therapy, diagnostics and imaging, although many challenges still need to be solved. However, for the application of gold nanoparticles (GNPs) in therapy and diagnostics it is necessary to know the bioaccumulation and local or systemic toxicity associated to them. The aim of the present study was to investigate the effects of intraperitoneal administration of GNPs on the histological alterations of the heart tissue of rats in an attempt to cover and understand the toxicity and the potential role of GNPs in the therapeutic and diagnostic applications. METHODS: Animals were randomly divided into 3 GNPs-treated rats groups and one control group (CG). The 10, 20 and 50 nm GNPs were administered intraperitonealy at the rate of 3 or 7 days as follows: Group 1: received infusion of 100 µl GNPs of size 10 nm for 3 or 7 days; Group 2: received infusion of 100 µl GNPs of size 20 nm for 3 or 7 days; Group 3: received infusion of 100 µl GNPs of size 50 nm for 3 or 7 days. CONTROL GROUP: received no GNPs. RESULTS: In comparison with the respective control rats, GNPs-treated rat received 100 µl of 10 and 20 nm particles for 3 days or 7 days demonstrating congested heart muscle with prominent dilated blood vessels, scattered and extravasations of red blood cells, focus of muscle hyalinosis, disturbed muscle fascicles, dense prominent focus of inflammatory cells infiltrate by small lymphocytes and few plasma cells while GNPs-treated rat received 100 µl of 50 nm particles for 3 or 7 days demonstrating benign normal looking heart muscle with normal muscle direction and fascicles, and very few scattered small lymphocytes. CONCLUSIONS: The histological alterations induced by intraperitoneal administration of GNPs were size-dependent with smaller ones induced more affects and related with time exposure of GNPs. This study suggests that interaction of GNPs with proteins and various cell types might be evaluated as part of the toxicological assessment in addition to further experiments related to tissues antioxidant enzymes, oxidative parameters, lipid peroxidation, production of free radicals and/or ROS and cytokine, histomorphologcal and ultrastrucural will be performed to cover and understand the toxicity and the potential use of GNPs as therapeutic and diagnostic tool.

Rheological and dielectric properties of different gold nanoparticle sizes.

BACKGROUND: Gold nanoparticles (GNPs) have found themselves useful for diagnostic, drug delivery and biomedicine applications, but one of the important concerns is about their safety in clinical applications. Nanoparticle size has been shown to be an extremely important parameter affecting the nanoparticle uptake and cellular internalization. The rheological properties assume to be very important as it affects the pressure drop and hence the pumping power when nano-fluids are circulated in a closed loop. The rheological and dielectric properties have not been documented and identified before. The aim of the present study was to investigate the rheology and the dielectric properties of different GNPs sizes in aqueous solution. METHODS: 10, 20 and 50 nm GNPs (Product MKN-Au, CANADA) was used in this study. The rheological parameters were viscosity, torque, shear stress, shear rate, plastic viscosity, yield stress, consistency index, and activation energy. These rheological parameters were measured using Brookfield LVDV-III Programmable rheometer supplied with temperature bath and controlled by a computer. RESULTS: The shear stress and shear rate of GNPs have shown a linear relationship and GNPs exhibited Newtonian behaviour. The GNPs with larger particle size (50 nm) exhibited more viscosity than those with smaller particle sizes (10 and 20 nm). Viscosity decreased with increasing the temperature for all the examined GNP sizes. The flow behaviour index (n) values were nearly ≤ 1 for all examined GNP sizes. Dielectric data indicated that the GNPs have strong dielectric dispersion in the frequency range of 20-100 kHz. The conductivity and relaxation time decreased with increasing the GNP size. CONCLUSIONS: This study indicates that the GNP size has considerable influence on the viscosity of GNPs. The strong dielectric dispersion was GNP size dependent. The decrease in relaxation time might be attributed to increase in the localized charges distribution within the medium confirmed by the conductivity data. This study suggests that further experiments are required to be done after the administration of GNPs through different routes in rats in vivo.