Increased inflammatory markers in brain and blood of rats subjected to acute homocysteine administration.
Hyperhomocysteinemia plays an etiologic role in the pathogenesis of disorders, including homocystinuria and neurodegenerative and cardiovascular diseases. In the present study, we studied the effect of acute administration of homocysteine, similar to that found in homocystinuria, on parameters of inflammation such as cytokines (TNF-alpha, IL-1beta and IL-6), chemokine CCL2 (MCP-1), nitrite and acute phase-proteins (C-reactive protein and alpha(1)-Acid glycoprotein) levels in brain and blood of rats. In addition, a differential count of blood leukocytes was performed. Wistar rats, aged 29 days, received a single subcutaneous injection of saline (control) or homocysteine (0.6 micromol/g body weight). Fifteen minutes, 1 h, 6 h or 12 h after the injection, the rats were sacrificed and serum, hippocampus and cerebral cortex were used. Results showed that homocysteine significantly increased proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and chemokine CCL2 (MCP-1) in serum, hippocampus and cerebral cortex. Nitrite levels also increased in hippocampus and cerebral cortex at 15 min, 1 h and 6 h, but not 12 h after homocysteine administration. Acute phase-protein levels were not altered by homocysteine. The percentage of neutrophils and monocytes significantly increased in blood at 15 min and 1 h, but not at 6 h and 12 h after acute hyperhomocysteinemia, when compared to the control group. Our results showed that acute administration of homocysteine increased inflammatory parameters, suggesting that inflammation might be associated, at least in part, with the neuronal and cardiovascular dysfunctions observed in homocystinuric patients.
da Cunha
Aline A
AA
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.
Ferreira
Andréa G K
AG
Wyse
Angela T S
AT
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006023:Glycoproteins / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage* / Q000097:blood; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D018836:Inflammation Mediators / Q000097:blood* / Q000378:metabolism; D007958:Leukocyte Count; D009961:Orosomucoid; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D001798:Blood Proteins; D018925:Chemokines; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; C506108:Orm1 protein, rat; D009961:Orosomucoid; D006710:Homocysteine; D002097:C-Reactive Protein