Abstract
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.
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.
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.
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.