title: Study of oxidative and inflammatory parameters in LDLr-KO mice treated with a hypercholesterolemic diet: Comparison between the use of Campomanesia xanthocarpa and acetylsalicylic acid.
abstract: BACKGROUND
  Atherosclerosis is an inflammatory disease that affects the arterial wall leading to myocardial, cerebral, and peripheral ischemic syndromes. The use of low doses of aspirin inhibits platelet aggregation and inflammation and prevents cardiovascular mortality. However, ASA may produce hemorrhagic events. Thus, several studies have sought new natural compounds to suppress platelet aggregation without causing serious adverse effects.
  
  
  OBJECTIVE
  In this sense, this study aims to compare the effects of Campomanesia xanthocarpa plant extract with those of acetylsalicylic acid (ASA) on inflammatory parameters observed in homozygous mice knockout for the low-density lipoprotein receptor (LDLr-KO) treated with a hypercholesterolemic diet.
  
  
  METHODS
  In this study, 28 male LDLr-KO mice were divided into three groups and fed a hypercholesterolemic diet for 4 weeks. Thereafter, the animals that received the hypercholesterolemic diet were treated for 5 days with (1) distilled water, (2) C. xanthocarpa extract, or (3) acetylsalicylic acid. The levels of inflammatory markers were assessed in the blood samples. The gastric tolerability of the animals after oral administration of the treatments was assessed through quantification of the lesions in the gastric mucosa.
  
  
  RESULTS
  The levels of proinflammatory cytokines IL-1, IL-6, TNF-α, and INF-γ were reduced to 19.2 ± 3%, 20.4 + 1.3%, 24.7 ± 1.2%, and 20.8 ± 1.7%, respectively, in the group treated with C. xanthocarpa, when compared to control group. Furthermore, treatment with plant extract significantly increased the levels of the anti-inflammatory cytokine IL-10 by 27.3 ± 5.9%, but ASA showed no significant effect on the same cytokines when compared to the control group, with the exception of IL-10, which presented an increase of 8.6 ± 3.5%. Treatments with C. xanthocarpa and ASA also caused significant reductions of 26.4 ± 3% and 38.4± 6% in the serum levels of oxLDL, respectively. However, only treatment with C. xanthocarpa reduced the levels of anti-oxLDL antibodies when compared with the control (25.8 ± 6%). In addition, the analyzed extract did not induce ulcerogenic activity, while ASA induced the formation of lesions.
  
  
  CONCLUSIONS
  In conclusion, treatment with C. xanthocarpa causes anti-inflammatory activity in hypercholesterolemic animals, with results superior to those obtained with the use of ASA.
authors.affiliation: Programa de Pós-Graduação em Atenção Integral à Saúde (PPGAIS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil. Electronic address: jonzeni@hotmail.com.
authors.forename: Jonatas Zeni
authors.initials: JZ
authors.lastname: Klafke
authors.affiliation: Programa de Pós-Graduação em Atenção Integral à Saúde (PPGAIS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Roberta Lelis Dias
authors.initials: RL
authors.lastname: Pereira
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Gabriela Elisa
authors.initials: GE
authors.lastname: Hirsch
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Mariana Migliorini
authors.initials: MM
authors.lastname: Parisi
authors.affiliation: Programa de Pós-Graduação em Atenção Integral à Saúde (PPGAIS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Fernando Garcez
authors.initials: FG
authors.lastname: Porto
authors.affiliation: Programa de Pós-Graduação em Atenção Integral à Saúde (PPGAIS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Amanda Spring
authors.initials: AS
authors.lastname: de Almeida
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Fabiane Horbach
authors.initials: FH
authors.lastname: Rubin
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil.
authors.forename: Henrique
authors.initials: H
authors.lastname: Beutler
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Nascimento
authors.affiliation: Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil; Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), 88006-000 Cricíuma, SC, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.affiliation: Programa de Pós-Graduacão em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Indiara
authors.initials: I
authors.lastname: Brusco
authors.affiliation: Programa de Pós-Graduacão em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: de Oliveira
authors.affiliation: Departamento de Ciências da Saúde, Universidade Luterana do Brasil, 97020 001 Santa Maria, RS, Brazil.
authors.forename: Marta Maria Medeiros Frescura
authors.initials: MM
authors.lastname: Duarte
authors.affiliation: Centro de ciências da saúde, Pós-Graduação em farmacologia Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Duarte
authors.affiliation: Programa de Pós-Graduação em Atenção Integral à Saúde (PPGAIS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Grupo Multidisciplinar de Saúde (GMS), Universidade de Cruz Alta (UNICRUZ), 98020-290 Cruz Alta, RS, Brazil; Centro de Ensino e Pesquisa (CEP), Instituto de Cardiologia de Cruz Alta (ICCA), 98010-110 Cruz Alta, RS, Brazil. Electronic address: vieciliprn@hotmail.com.
authors.forename: Paulo Ricardo Nazário
authors.initials: PR
authors.lastname: Viecili
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy*; D001938:Brazil; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D027822:Myrtaceae / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D008077:Lipoproteins, LDL; D010936:Plant Extracts; D001241:Aspirin
keywords: Cytokines; High performance liquid chromatography; Inflammation; Interleukins; Medicinal plant; Phenolic compounds