title: Chronic hyperhomocysteinemia increases inflammatory markers in hippocampus and serum of rats.
abstract: This study investigated the effects of chronic homocysteine administration on some parameters of inflammation, such as cytokines (TNF-α, IL-1β and IL-6), chemokine CCL(2) (MCP-1), nitrite and prostaglandin E(2) levels, as well as on immunocontent of NF-κB/p65 subunit in hippocampus and/or serum of rats. Since acetylcholinesterase has been associated with inflammation, we also evaluated the effect of homocysteine on this enzyme activity in hippocampus of rats. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 μmol/g body weight) or saline (control) from the 6th to the 28th days-of-age. One or 12 h after the last injection, rats were euthanized and hippocampus and serum were used. Results showed that chronic hyperhomocysteinemia significantly increased pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), chemokine CCL(2) (MCP-1) and prostaglandin E(2) in hippocampus and serum of rats at 1 and 12 h after the last injection of homocysteine. Nitrite levels increased in hippocampus, but decreased in serum at 1 h after chronic hyperhomocysteinemia. Acetylcholinesterase activity and immunocontent of citoplasmic and nuclear NF-κB/p65 subunit were increased in hippocampus of rats subjected to hyperhomocysteinemia at 1 h, but did not alter at 12 h after the last injection of homocysteine. According to our results, chronic hyperhomocysteinemia increases inflammatory parameters, suggesting that this process might be associated, at least in part, with the cerebrovascular and vascular dysfunctions characteristic of some homocystinuric patients.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: da Cunha
authors.forename: Andréa G K
authors.initials: AG
authors.lastname: Ferreira
authors.forename: Samanta O
authors.initials: SO
authors.lastname: Loureiro
authors.forename: Maira J
authors.initials: MJ
authors.lastname: da Cunha
authors.forename: Felipe
authors.initials: F
authors.lastname: Schmitz
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D006624:Hippocampus / Q000378:metabolism*; D006712:Homocystinuria / Q000150:complications / Q000503:physiopathology; D020138:Hyperhomocysteinemia / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D009573:Nitrites; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000110:Acetylcholinesterase; D015232:Dinoprostone