Effect of acute and long-term administration of gold nanoparticles on biochemical parameters in rat brain.

The present study investigated stress oxidative parameters and activities of enzymes of the energy metabolism in various brain structures. Rats were subjected to acute and long-term administration of gold nanoparticles (GNPs) with mean diameters of 10nm and 30nm. Adult (60days old) male Wistar rats received a single intraperitoneal injection (acute administration; 70µg·kg-1) or repeated injections once daily for 28days (long-term administration; 70µg·kg-1) of saline solution or GNPs (10nm or 30nm). Twenty-four hours after administration of the final dose, the animals were killed and the cerebral structures were isolated for enzyme analysis. In this study, we observed that the thiobarbituric acid-reactive species and carbonyl protein levels were decreased after acute administration of GNPs, whereas the superoxide dismutase activity was increased after acute and long-term of GNPs. The catalase activity was affected by the administration of GNPs. Furthermore, we have not found change in the citrate synthase activity. The succinate dehydrogenase, malate dehydrogenase, complexes I, II, II-III and IV, and creatine kinase activities were altered. These results indicate that inhibition energy metabolism can be caused by oxidative stress.

Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one.