Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

Silver (Ag) and gold nanoparticles (Au NPs) have wide applications. They are increasingly being used in the medical devices, biosensors, cancer cell imaging, and cosmetics. Increased applications of these NPs in the technological advances have also led to the risk of exposure to these particles. This study investigated the toxic effects of Ag and Au NPs (1 μM and 2 μM, oral) on mouse erythrocytes and tissues after 14 consecutive days' exposure. Our results demonstrate significant increase in reactive oxygen species (ROS) and depletion of antioxidant enzyme status in erythrocytes and tissues. Hepatic and renal toxicity was evident from liver and kidney function tests. Inflammatory markers, interleukin-6 and nitric oxide synthase increased in plasma on administration following exposure to these NPs at both the doses. A more pronounced increase was noted in kidney metallothionein (MT) compared to liver MT on exposure to these NPs. Toxic potential of these NPs was further confirmed by increased 8-hydroxy-2'-deoxyguanosine levels in urine, a biomarker of DNA damage. Among the two NPs, Ag NP was more toxic at 2 μM dose compared to lower dose of 1 μM. The study suggests oxidative stress as the major mechanism responsible for the toxic manifestations induced by Ag and Au NPs.

Heavy metals are known to cause oxidative deterioration of bio-molecules by initiating free radical mediated chain reaction resulting in lipid per-oxidation, protein oxidation and oxidation of nucleic acid like DNA and RNA. The development of effective dual functioning antioxidants, possessing both metal-chelating and free radical-scavenging properties should bring into play. Administration of natural and synthetic antioxidants like, quercetin, catechin, taurine, captopril, gallic acid, melatonin, N-acetyl cysteine, α- lipoic acid and others have been recognized in the disease prevention and clinical recovery against heavy metal intoxication. These antioxidants affect biological systems not only through direct quenching of free radicals but also via chelation of toxic metal(s). These antioxidants also, have the capacity to enhance cellular antioxidant defense mechanism by regenerating endogenous antioxidants, such as glutathione and vitamin C and E. They also influence cellular signaling and trigger redox sensitive regulatory pathways. The reactivity of antioxidants in protecting against heavy metal induced oxidative stress depends upon their structural properties, their partitioning abilities between hydrophilic and lipophilic environment and their hydrogen donation antioxidant properties. Herein, we review the structural, biochemical and pharmacological properties of selected antioxidants with particular reference to their ability to (i) chelate heavy metals from its complex (ii) ameliorate free radical (iii) terminate heavy metal induced free radical chain reaction (iv) regenerate endogenous antioxidants and, (v) excretion of metal without its redistribution.

Introduction: Exposure to nanomaterials (NPs) may lead to enhanced generation of free radicals and failure of endogenous antioxidant defense system ultimately resulting in oxidative stress. The present study aimed to evaluate the comparative efficacy of alpha lipoic acid (ALA) and quercetin, the two antioxidants against aluminium oxide nanoparticle induced oxidative stress. Methods and Materials: Male swiss albino mice were exposed to aluminum oxide NPs for seven days and were co-administered orally with quercetin and alpha lipoic acid (50 mg/kg each) to evaluate effects on heme synthesis pathway, hepatic oxidative injury and antioxidant potential. Results: The results suggest a significantly elevated ROS, decreased blood and hepatic GSH levels, Superoxide dismutase and Catalase activities after Al 2 O 3 nanoparticles exposure. Co-administration of antioxidants increased GSH levels and was also beneficial in the recovery of oxidative injury and restoring inhibited ALAD activity. Conclusion: Our results suggest better efficacy of alpha lipoic acid than Quercetin in preventing appearance of toxic symptoms of following exposure to Al 2 O 3 nanoparticles in mice.