The potential role of sulfur amino acids in the acute inflammatory response

Abstract

The sulfur amino acids (SAA), methionine (Met) and cysteine (Cys) have an important role in the acute inflammatory response, including regulating the production of reactive oxygen species (ROS) and the development of cardiovascular disease (CVD). The objectives of the current study were 1) study alterations in Met cycle on the acute inflammatory response 2) investigate the in vivo temporal changes induced by an intraperitoneal (IP) injection of lipopolysaccharide (LPS), and 3) identify the potential effect of altered dietary SAA on the acute inflammatory response in male Wistar rats. The LPS dose that induced inflammation to a greater extent was 100 μg/kg compared with 50 μg/kg. LPS at 100 μg/kg presented a significant increase in both temperatures (p<0.05) and cytokine tumor necrosis factor-alpha (TNF-α) (p<0.001) post-injection compared with control. Additionally, at a dose of 100 μg/kg showed a significant increase in temperature when compared with 50 μg/kg at 120min (p<0.05) and 240 min (p<0.05). Plasma biochemical analyses revealed that the TNF-α area under the curve in dietary SAA of 50Met:50Cys was significantly higher (p<0.004) when compared with a dietary SAA ratio of 100Met:0Cys; however, no significant differences were observed in the percentage of leukocytes that were neutrophils. Additionally, a diet with a balanced Met:Cys ratio increased concentrations of plasma Cys and glutathione (GSH) after 4h. Adequate dietary intake of SAA play an important role in the immune response synthetizing intracellular antioxidant including GSH. An increase in the requirement of SAA or impairment in the SAA metabolism under infection can affect negatively the production of pro-inflammatory cytokines such as TNF-α, IL-6 and neutrophil proliferation. Perturbations in the transmethylation (TM) and transsulfuration (TS) pathways can lead to hyperhomocysteinemia (HHcy; plasma homocysteine >15 µmol/L) increasing the risk of coronary artery disease or kidney failure. Overall, the results presented in this study serve to highlight the potential effect of altered dietary SAA ratio in a model of systemic inflammatory response syndrome in addition to demonstrating the potential negative effect of impairment in the SAA metabolism.