Effect of treatment with gold nanoparticles on protein expression of oxidative and inflammatory markers in mice brain or blood cells with sepsis-associated encephalopathy and glioblastoma multiforme

• Grant number: 17/01762-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2017
• End date: August 19, 2017
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Stephen Fernandes de Paula Rodrigues
• Grantee: Luis Guilherme Xavier Fernandes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/05146-6 - Therapeutical efficacy of gold nanoparticles to glioblastoma multiform or septic encephalopathy in mice, AP.JP

Abstract

Among the most serious CNS-affecting disease are glioblastoma multiforme and septic encephalopathy. By 4% of all cancers in Brazil are placed in the CNS, being glioblastoma multiforme one of the most aggressive and fatal (OMURO & DEANGELIS, 2013). It is also frequent the number of people with septic encephalopathy. They are around 71% of septic shock-diagnosed patients (PAPADOPOULOS et al., 2000). As key factors for the full development of those diseases are inflammation and oxidative stress (BALKWILL & MANTOVANI, 2001; SIAMI et al., 2008). Gold nanoparticles (AuNPs) own great potential for combating those diseases, once they have intrinsic anti-inflammatory and antioxidant properties (UCHIYAMA et al. 2014). Then, we propose studying the effect of AuNPs treatment on the expression of inflammation and oxidative stress markers in glioblastoma multiforme- or septic encephalopathy-induced mice. For that, sepsis will be induced using the cecal ligation and perforation model, and glioblastoma multiforme will be got by local injection (in the brain) of the glioblastoma cell line, GL261. Mice will be treated intravenously (IV), with AuNPs-cit or AuNPs-IgG (10^12 particles/mL). As three control solutions for the AuNP treatments are: 1) antibody anti-H3.3 solution, which was used to prepare the AuNPs-IgG; 2) sodium aurothiomalate (Sigma-Aldrich), in an anti-inflammatory dose, 0.7 ¼g/g body weight, dissolved in saline, according to SIN & WONG (1992); or 3) saline; all given once, IV, two or four hours after sepsis induction, or in alternate days for 20 days, beginning seven days after tumor induction. Six hours after sepsis induction or 20 days after beginning of treatment of glioblastoma multiforme-carrying mice, animals will be euthanized and brain harvested and frozen (-80oC) for further measurement of protein expression of: iNOS and gp91phox for septic brains, or proliferating cell nuclear antigen (PCNA) and epidermal growth factor for brain-containing tumor, by western blotting. Besides, blood from those animals will be harvested for measurement of protein expression of L-selectin and CD18 in leukocytes, and P-selectin and alpha(IIb)beta(3) integrin in platelets, by flow citometry. (AU)