The oral administration of silver nanoparticles activates the kynurenine pathway in rat brain independently of oxidative stress

Abstract

In this work, we determined whether oxidative stress contributed to the activation of the kynurenine pathway by AgNPs. Male Wistar rats weighing between 130 and 146 g were randomly assigned into six groups. Animals in the negative control group were orally administered distilled water while, the other treatment groups were respectively given AgNPs (25 and 50 mg/kg bw) alone or in combination with Trolox (100 mg/kg bw). Results showed that treatments with AgNPs significantly raised protein carbonyl level in rat liver, but the co-treatment with Trolox attenuated the elevation. Conversely, AgNPs raised the level of reduced glutathione (GSH) in rat plasma and tissues compared to the negative control. Further, oral exposure to AgNPs (50 mg/kg bw) significantly elevated rat plasma and brain kynurenine levels compared to the negative control. Meantime, the cotreatment with Trolox appreciably restored kynurenine level in rat plasma, but not in the rat brain. Taken together, findings indicate that the oral administration of AgNPs alone at the doses used in this study, might not have caused oxidative stress. However, the co-treatment with Trolox appears to potentiate oxidative stress in rats following exposure to AgNPs. Furthermore, data support that the activation of the kynurenine pathway in the rat brain by AgNPs might be independent of oxidative stress. The findings are new and contribute to deepen our understanding of the cellular interaction by nanoparticles.

Differential Immunomodulatory Potential of Silver Nanoparticles and Effect on the Kynurenine Pathway in Male Wistar Rats

“…More so, the kynurenine pathway can be activated in presence of oxidative stress and inflammation [11]. In contrast, recent studies revealed that kynurenine pathway activation in the rat brain by AgNPs was independent of oxidative stress [11]. This finding may indicate that kynurenine pathway activation in the rat brain may be through other means including the inflammatory signalling processes.…”

“…Together, these facts link free radical production and cytokine modulation to kynurenine pathway activation [10]. More so, the kynurenine pathway can be activated in presence of oxidative stress and inflammation [11]. In contrast, recent studies revealed that kynurenine pathway activation in the rat brain by AgNPs was independent of oxidative stress [11].…”

Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway

“…Where appropriate, biochemical assays were performed by a spectrophotometric method using a UV/Vis spectrophotometer (Jenway, Staffordshire, United Kingdom). The test for kynurenine followed an established protocol [ 19 ]. Methods to determine the nitric oxide level (nitrite/nitrate concentration) and the total antioxidant capacity (TAC) are described elsewhere [ 20 ].…”

Hypoxia and the Kynurenine Pathway: Implications and Therapeutic Prospects in Alzheimer’s Disease

“…Also, the imbalance in reactive oxygen species (ROS) produced results in oxidative stress and dysfunction in axoplasmic transport and, eventually, neuronal cell death [ 13 ]. Furthermore, compromised redox homeostasis resulting from hypoxia and kynurenine pathway activation [ 14 , 15 ] plays a role in neurodegeneration [ 16 , 17 ]. Discussed below are the major factors or conditions contributing to neurodegeneration.…”