Increased inflammatory markers in brain and blood of rats subjected to acute homocysteine administration

Abstract

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.

Hyperhomocysteinaemia predicts the decline in pulmonary function in healthy male smokers

“…SEEMUNGAL et al [15] also reported an association between homocysteine levels and C-reactive protein levels in COPD patients. Acute administration of homocysteine to rats is reported to result in elevated blood and brain concentrations of cytokines [34]. This suggests that hyperhomocysteinaemia may partly contribute to the systemic inflammation observed in COPD patients.…”

Plasma Homocysteine Concentrations in Dogs

“…They concluded that impaired folate metabolism may underlie the development of atopy. There are, however, many papers that suggest that Hcy stimulates the immune system via NF-κB activation (da Cunha et al, 2010 (Schroecksnadel et al, 2003). Rossi et al, (2008) reported that Hcy is a useful biomarker of canine renal disorders.…”

Pathological concentrations of homocysteine increases IL-1β production in macrophages in a P2X7, NF-ĸB, and erk-dependent manner

“…High plasma levels of Hcy are likely related to the enhanced production of pro-inflammatory cytokines, including IL-1β [5][6][7]. However, the mechanisms underlying the effects of Hcy on immune cells are not completely understood.…”

“…In this context, the NF-κB pathway is a central element involved in IL-1β synthesis [25]. Previous data has shown that acute hyperhomocysteinemia increases NF-κB/ p65 subunit expression in rat hippocampi, as well as the serum levels of TNF-α, IL-1β, IL-6, and CCL2 (MCP-1) [26,5]. Furthermore, ERK activation in murine macrophages has been associated with the pathological effects of Hcy, such as an increase in metalloproteinase 9 production [27].…”