TITLE OF PUBLICATION:The Oral Administration of Silver Nanoparticles activates the Kynurenine pathway in rat brain independently of oxidative stress

JOURNAL: Chemico-Biological Interactions


AUTHORS: Oluyomi Stephen Adeyemi, Rhoda Ananu Uloko, Oluwakemi Josephine Awakan, Anne Adebukola Adeyanju, David Adeiza Otohinoyi

What is it about? 

The use of silver nanoparticles for biomedical purposes is steadily increasing and has been gaining wider attraction. However, the limited knowledge about cellular targets or interaction of these nanoparticles remains a challenge that impedes full exploration of the biomedical prospects of nanotechnology. Nonetheless, there are emerging evidence suggesting that nanoparticles have multiple cellular targets, among which are the activation of the kynurenine pathway as well as the production of reactive oxygen species (ROS) leading to oxidative stress. Interestingly, ROS and/or oxidative stress has been strongly linked with the oxidative degradation of L-tryptophan to form kynurenine. However, we do not know yet whether silver nanoparticles activate the kynurenine pathway by facilitating oxidative stress and/or ROS production. Therefore, in this work, we examined the involvement of oxidative stress in relation to the activation of the kynurenine pathway by silver nanoparticles in Wistar rats.

Why is it important? 

Not only is the advancement in nanotechnology witnessing a great surge in recent times, but the biomedical application of nanoparticles and or nanomaterials has continued to attract increasing attention. However, as the research community continues to celebrate and explore the remarkable prospects of nanoparticles for biomedical applications, our current knowledge and understanding of the mechanistic behavior of these nanomaterials in living cells are limited. Therefore, as a proof of concept, this work determined and confirmed that silver nanoparticles activated the kynurenine pathway independently of oxidative stress in Wistar rats.

What are the new discoveries from the research? 

The findings in this work glean new perspective about the mechanistic behavior of nanoparticles in living cells. Additionally, the data are in a part a contribution that deepens our understanding of the cellular interaction of nanoparticles, thereby informing the direction of our future investigations in this regard.


In this work, we determined whether oxidative stress contributed to the activation of the kynurenine pathway by silver nanoparticles (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 co-treatment 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.

Article DOI: 10.1016/j.cbi.2019.01.034

ArticleURL: https://www.sciencedirect.com/science/article/pii/S0009279718313863?via%3Dihub

ArticleLMU Repository Link: https://eprints.lmu.edu.ng/cgi/users/home?screen=EPrint%3A%3AView&eprintid=1077

Lead AuthorResearchgate Link: https://www.researchgate.net/profile/Oluyomi_Adeyemi?ev=hdr_xprf&_sg=9peau0ux1-5tGqEzfLmuZgG9pzonraOZE1i2s0fgWyQD9X5HHOPu75BZovzLqqIRomSegv_4u8g4dJzaB_4-yy0Z

Lead AuthorScopus Link: https://www.scopus.com/authid/detail.uri?authorId=55353836900

LeadAuthor Linkedln Link: https://www.linkedin.com/in/oluyomi-adeyemi-09123446/

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