Toxicological Alterations Induced by Subacute Exposure of Cobalt Oxide Nanoparticles in Aged Rats: Behavioral, Biochemical, Molecular, and Histopathological Evidence.

Abstract

Currently, evidence has pointed out that metal-based nanomaterials may have potentially harmful outcomes in the development of such diseases related to neurodegenerative disorders, oxidative stress, and inflammation. Among them, cobalt oxide nanoparticles (Co3O4-NPs), nano metal-oxides, are widely used in several areas such as industries and as wastewater treatment. Although Co3O4-NPs have a large scale in biological and industrial applications, there is a growing concern to their toxic effect on human health and the environment due to their reduced size and high reactivity, both chemically and biologically. The present work investigated the potential toxic outcomes of cobalt nanoparticles on cognitive performance in aged rats, focusing on the mechanisms involved in the oxidative stress and inflammation-related process. In our study, aged (18-month-old) Wistar male rats were used to study the harmful effects of subacute cobalt nanoparticles (Co3O4-NPs) (1 and 4 mg/kg bw.S.C.28 days) on the cortex and striatum. The characterization revealed that the CO3O4-NPs sample consists of extremely small particles with a semi-spherical shape. Exposure of aged rats to Co3O4-NPs induced an elevation of indicators oxidative injury [protein oxidation (PCO), malondialdehyde (MDA), and advanced oxidation protein products (AOPP)] and nitrosative stress markers [nitrite production (NO)]. This effect was accompanied by a decrease in the activities of CAT, SOD, and GPx, as well as a reduction in the level of glutathione (GSH) and non-protein thiols (NPSH). Exposure of aged rats to Co3O4-NPs resulted also in the overexpression of pro-inflammatory markers (TNF-α, IL-6, and.. NF-kB) in the cortex and striatum. In addition, Co3O4-NPs exhibited cognitive deficits in the Novel Object Recognition Test (NORT), as demonstrated by a decrease in the discrimination index. Heightened anxiety-like behavior was also observed in the Marble Burying test (MBT) and Open-field test (OFT), along with depressive-like behavior, as evidenced by prolonged immobility durations in the tail suspension test (TST) and Forced swimming test (FST). The histopathological analysis revealed changes in the striatum and cortex regions of the treated aged rats characterized by the presence of vacuolated and shrunken neurons. In summary, these findings highlight the susceptibility of the aging brain to Co3O4-NPs-induced neurotoxicity and underscore the role of oxidative stress and neuroinflammation as critical drivers of these effects.