Journal
JOURNAL OF DRUG TARGETING
Volume 28, Issue 4, Pages 428-436Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/1061186X.2019.1678168
Keywords
Sepsis; brain; gold nanoparticles; n-acetylcysteine; oxidative stress
Categories
Funding
- National Council for Scientific and Technological Development (CNPq)
- Coordination for the Improvement of Higher Education Personnel (CAPES)
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Herein, we report the effect of gold nanoparticles (AuNP) and n-acetylcysteine (NAC) isolated or in association as important anti-inflammatory and antioxidant compounds on brain dysfunction in septic rats. Male Wistar rats after sham operation or caecal ligation and perforation (CLP) were treated with subcutaneously injection of AuNP (50?mg/kg) and/or NAC (20?mg/kg) or saline immediately and 12?h after surgery. Twenty-four hours after CLP, hippocampus and prefrontal cortex were obtained and assayed for myeloperoxidase (MPO) activity, cytokines, lipid peroxidation, protein carbonyls formation, mitochondrial respiratory chain, and CK activity. AuNP?+?NAC association decreased MPO activity and pro-inflammatory cytokines production, being more effective than NAC or AuNP isolated treatment. AuNP?+?NAC association and NAC isolated treatment decreased oxidative stress to lipids in both brain structures, while protein oxidation decreased only in the hippocampus of AuNP?+?NAC association-treated animals. Complex I activity was increased with AuNP?+?NAC association and NAC isolated in the hippocampus. Regarding CK activity, AuNP and AuNP?+?NAC association increased this marker in both brain structures after CLP. Our data provide the first experimental demonstration that AuNP and NAC association was able to reduce sepsis-induced brain dysfunction in rats by decreasing neuroinflammation, oxidative stress parameters, mitochondrial dysfunction and CK activity.
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