PMID- 36139733 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220928 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 11 IP - 9 DP - 2022 Aug 26 TI - Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways. LID - 10.3390/antiox11091659 [doi] LID - 1659 AB - BACKGROUND: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. METHODS: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. RESULTS: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GC-resistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases delta (PI3Kdelta) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. CONCLUSION: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2. FAU - Serra, Magda F AU - Serra MF AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Cotias, Amanda C AU - Cotias AC AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Pimentel, Andreza S AU - Pimentel AS AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Arantes, Ana Carolina S de AU - Arantes ACS AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Pires, Ana Lucia A AU - Pires ALA AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Lanzetti, Manuella AU - Lanzetti M AUID- ORCID: 0000-0003-3913-608X AD - Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil. FAU - Hickmann, Jandir M AU - Hickmann JM AUID- ORCID: 0000-0003-0310-4190 AD - Institute of Physics, Federal University of Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil. FAU - Barreto, Emiliano AU - Barreto E AUID- ORCID: 0000-0002-4956-5075 AD - Laboratory of Cell Biology, Federal University of Alagoas, Maceio 50072-900, AL, Brazil. FAU - Carvalho, Vinicius F AU - Carvalho VF AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Silva, Patricia M R E AU - Silva PMRE AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Cordeiro, Renato S B AU - Cordeiro RSB AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. FAU - Martins, Marco Aurelio AU - Martins MA AD - Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil. LA - eng GR - E-26/010.000983/2019/FAPERJ/ PT - Journal Article DEP - 20220826 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC9495660 OTO - NOTNLM OT - HDAC2 OT - NRF2 OT - gold nanoparticle OT - lung inflammation OT - oxidative imbalance OT - steroid-insensitive asthma COIS- The authors declare no competing financial interests or personal relationships that could have influenced the work reported in this paper. EDAT- 2022/09/24 06:00 MHDA- 2022/09/24 06:01 PMCR- 2022/08/26 CRDT- 2022/09/23 01:08 PHST- 2022/07/01 00:00 [received] PHST- 2022/08/19 00:00 [revised] PHST- 2022/08/21 00:00 [accepted] PHST- 2022/09/23 01:08 [entrez] PHST- 2022/09/24 06:00 [pubmed] PHST- 2022/09/24 06:01 [medline] PHST- 2022/08/26 00:00 [pmc-release] AID - antiox11091659 [pii] AID - antioxidants-11-01659 [pii] AID - 10.3390/antiox11091659 [doi] PST - epublish SO - Antioxidants (Basel). 2022 Aug 26;11(9):1659. doi: 10.3390/antiox11091659.