Mohamed Anwar K Abdelhalim

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

BackgroundNanoparticles (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.MethodsTo 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).ResultsIn 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.ConclusionsThe 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.

Identification of potential biomarkers of gold nanoparticle toxicity in rat brains

BackgroundGold 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.MethodsMale 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.ResultsIn 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.ConclusionThis 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.

Gold nanoparticles administration induced prominent inflammatory, central vein intima disruption, fatty change and Kupffer cells hyperplasia

BackgroundAdvances in nanotechnology have identified promising candidates for many biological, biomedical and biomedicine applications. They are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the effects of administration of gold nanoparticles (GNPs) on inflammatory cells infiltration, central vein intima disruption, fatty change, and Kupffer cells hyperplasia in the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use.MethodsA total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of 10, 20 and 50 nm GNPs for 3 or 7 days. Animals were randomly divided into groups, 12 GNPs-treated rats groups and one control group (NG). Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days), size 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively.ResultsIn comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis. In addition, inflammatory cell infiltration, Kupffer cells hyperplasia, central veins intima disruption, hepatic strands dilatation and occasional fatty change together with a loss of normal architechiture of hepatic strands were also seen.ConclusionsThe alterations induced by the administration of GNPs were size-dependent with smaller ones induced more affects and related with time exposure of GNPs. These 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 histological alterations 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 necrosis.

Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver

BackgroundNanoparticles (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. The aim of the present study was to investigate the particle-size, dose and exposure duration effects of gold nanoparticles (GNPs) on the hepatic tissue in an attempt to cover and understand the toxicity and their potential therapeutic and diagnostic use.MethodsA 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) to investigate particle-size, dose and exposure duration effects of GNPs on the hepatic tissue.ResultsIn 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 vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis.ConclusionsThe hepatocytes swelling might be exhibited as a result of disturbances of membranes function that lead to massive influx of water and Na+ due to GNPs effects accompanied by leakage of lysosomal hydrolytic enzymes that lead to cytoplasmic degeneration and macromolecular crowding. Hydropic degeneration is a result of ion and fluid homestasis that lead to an increase of intracellular water. The vacuolated swelling of the cytoplasm of the hepatocytes of the GNPs treated rats might indicate acute and subacute liver injury induced by the GNPs. Binucleation represents a consequence of cell injury and is a sort of chromosomes hyperplasia which is usually seen in regenerating cells. 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 role as a therapeutic and diagnostic tool.

Physical Properties of Different Gold Nanoparticles: Ultraviolet-Visible and Fluorescence Measurements

Background: The light absorption and emission characteristics of Gold Nanoparticles (GNPs) are exploited in detection and treatment of cancer. The properties of Nanoparticles (NPs) give them high potential for use in various medical applications, particularly in diagnostics and therapy where they promise increased sensitivity, speed, and costeffectiveness. The Ultraviolet-Visible and fluorescence properties of non-functionalized GNPs have not thus far been comprehensively documented. This study evaluated the absorption and fluorescence spectra for solutions of GNPs at different concentrations. Methods: The mean sizes of these GNPs were calculated from Transmission Electron Microscope (TEM) images, which were also used to study the morphology of the GNPs. UV–Visible and fluorescence measurements, were made from 250-700 nm using 1 cm quartz cuvettes. Results: When the GNP size changed from 10 nm to 50 nm, the maximum extinction of the Surface Plasmon Band (SPB) shifted from 517 nm to 532 nm in the visible region which may be attributed to the surface plasmon oscillation of free electrons. At constant GNP size, the absorbance was found to be proportional to the concentration of gold. This is because an increased number of GNPs also increases the total surface for surface plasmon resonance. The Photoluminescence (PL) band centre appears at 423 nm. An increase in fluorescence intensity with increase in GNP size was observed. At a fixed GNP size of 10 nm, and with increasing GNP concentration, the intensity of the emission band increased, which was consistent with the changes observed for the surface plasmon band of GNPs. Conclusions: The absorption intensity and maxima are particle size dependent. The surface plasmon resonance of the gold particles is red shifted (from 517 to 532 nm) with increasing particle size. These results indicate that the fluorescence intensity and the absorption band of GNPs were concentration and particle size dependent.

Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles.

BackgroundGold nanoparticles (GNPs) have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs) are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity.MethodsA total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days) to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days), size 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs.ResultsIn comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones.ConclusionsThe induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS) generation which in turn may induce stress in the renal cells to undergo atrophy and necrosis. The produced alterations were size-dependent with smaller ones induced more affects and related with time exposure of GNPs.

The appearance of renal cells cytoplasmic degeneration and nuclear destruction might be an indication of GNPs toxicity

BackgroundAdvances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of nanoparticles (NPs) differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The histological and the histochemical alterations in the renal tissues due to gold nanoparticles (GNPs) have not well documented and have not yet been identified. The aim of the present study was to investigate the particle-size effect of GNPs on the renal tissue in an attempt to address their potential toxicity.MethodsA total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days) to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days), size 20 nm (3 or 7 days) and 50 nm (3 or 7 days), respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively.ResultsThe histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling and renal tubular necrosis. Interstitial alterations included: intertubular blood capillaries dilatation, intertubular hemorrhage and inflammatory cell infiltrations. The glomeruli showed moderate congestion with no hypercelluraity and mesangial proliferation or basement membrane thickening.ConclusionsThe induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that become 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 more effects and related with time exposure of GNPs. The produced histological alterations may suggest that GNPs interact with proteins and enzymes of the renal tissue interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS) generation which in turn may induce stress in the renal cells to undergo atrophy and necrosis. More histomorphologcal investigations are needed to address the potential threat of GNPs as a therapeutic and diagnostic tool.

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

BackgroundCurrent 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.MethodsAnimals 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.ResultsIn 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.ConclusionsThe 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.

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

BackgroundDespite 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.MethodsA 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.ResultsIn 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.ConclusionsThe 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

BackgroundOne 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.MethodsThe 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.ResultsAfter 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.ConclusionsThe 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.