Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals

Abstract We hypothesized whether propofol or active propofol component (2,6‐diisopropylphenol [DIPPH] and lipid excipient [LIP‐EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receiv...

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Autores principales: Luciana Boavista Barros Heil, Fernanda Ferreira Cruz, Mariana Alves Antunes, Cassia Lisboa Braga, Lais Costa Agra, Rebecca Madureira Bose Leão, Soraia Carvalho Abreu, Paolo Pelosi, Pedro Leme Silva, Patricia Rieken Macedo Rocco
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Publicado: Wiley 2021
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spelling oai:doaj.org-article:a7044bc4b9fa4625b8ff2b85bdfb27b42021-11-16T13:45:55ZEffects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals2052-170710.1002/prp2.873https://doaj.org/article/a7044bc4b9fa4625b8ff2b85bdfb27b42021-10-01T00:00:00Zhttps://doi.org/10.1002/prp2.873https://doaj.org/toc/2052-1707Abstract We hypothesized whether propofol or active propofol component (2,6‐diisopropylphenol [DIPPH] and lipid excipient [LIP‐EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receive a standard (lean) or obesity‐inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6‐DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL‐6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL‐6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95–5.20]; p = .04) and its active component (2,6‐DIPPH) (4.09[1.67–5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6‐DIPPH increased IL‐10 expression (7.59[6.28–12.95]; p = .001) in adipose tissue‐derived macrophages. Additionally, 2,6‐DIPPH increased C‐X‐C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23–29.01]; p = .02; 1.55[1.49–3.43]; p = .02) and adipose tissues (8.78[4.15–11.57]; p = .03; 2.86[2.17–3.71]; p = .01), as well as improved lung‐derived neutrophil migration (28.00[−3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.Luciana Boavista Barros HeilFernanda Ferreira CruzMariana Alves AntunesCassia Lisboa BragaLais Costa AgraRebecca Madureira Bose LeãoSoraia Carvalho AbreuPaolo PelosiPedro Leme SilvaPatricia Rieken Macedo RoccoWileyarticleadipose tissueinflammationlungmacrophagesneutrophilsobesityTherapeutics. PharmacologyRM1-950ENPharmacology Research & Perspectives, Vol 9, Iss 5, Pp n/a-n/a (2021)
institution DOAJ
collection DOAJ
language EN
topic adipose tissue
inflammation
lung
macrophages
neutrophils
obesity
Therapeutics. Pharmacology
RM1-950
spellingShingle adipose tissue
inflammation
lung
macrophages
neutrophils
obesity
Therapeutics. Pharmacology
RM1-950
Luciana Boavista Barros Heil
Fernanda Ferreira Cruz
Mariana Alves Antunes
Cassia Lisboa Braga
Lais Costa Agra
Rebecca Madureira Bose Leão
Soraia Carvalho Abreu
Paolo Pelosi
Pedro Leme Silva
Patricia Rieken Macedo Rocco
Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
description Abstract We hypothesized whether propofol or active propofol component (2,6‐diisopropylphenol [DIPPH] and lipid excipient [LIP‐EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receive a standard (lean) or obesity‐inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6‐DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL‐6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL‐6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95–5.20]; p = .04) and its active component (2,6‐DIPPH) (4.09[1.67–5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6‐DIPPH increased IL‐10 expression (7.59[6.28–12.95]; p = .001) in adipose tissue‐derived macrophages. Additionally, 2,6‐DIPPH increased C‐X‐C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23–29.01]; p = .02; 1.55[1.49–3.43]; p = .02) and adipose tissues (8.78[4.15–11.57]; p = .03; 2.86[2.17–3.71]; p = .01), as well as improved lung‐derived neutrophil migration (28.00[−3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.
format article
author Luciana Boavista Barros Heil
Fernanda Ferreira Cruz
Mariana Alves Antunes
Cassia Lisboa Braga
Lais Costa Agra
Rebecca Madureira Bose Leão
Soraia Carvalho Abreu
Paolo Pelosi
Pedro Leme Silva
Patricia Rieken Macedo Rocco
author_facet Luciana Boavista Barros Heil
Fernanda Ferreira Cruz
Mariana Alves Antunes
Cassia Lisboa Braga
Lais Costa Agra
Rebecca Madureira Bose Leão
Soraia Carvalho Abreu
Paolo Pelosi
Pedro Leme Silva
Patricia Rieken Macedo Rocco
author_sort Luciana Boavista Barros Heil
title Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
title_short Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
title_full Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
title_fullStr Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
title_full_unstemmed Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
title_sort effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals
publisher Wiley
publishDate 2021
url https://doaj.org/article/a7044bc4b9fa4625b8ff2b85bdfb27b4
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