Alteration of the dietary methionine: Cysteine ratio modulates the inflammatory response to an inter-peritoneal injection of lipopolysaccharide in wistar rats

Abstract

Sulphur amino acids (SAA) are essential for multiple physiological/metabolic processes, with the ratio of dietary methionine: cysteine (Met:Cys) being an important contributor to pro-inflammatory responses, including TNF-α activity. The current study was designed to determine the effect an altered dietary SAA ratio, and the resulting reliance on the transsulfuration pathway to supply Cys, will have on the inflammatory response. In the present study, 100 µg/kg of an intraperitoneal (IP) injection of lipopolysaccharide (LPS) was used as a model for systemic inflammation. Male Wistar rats were randomized to one of two amino acid-defined diets, (100Met:0Cys or 50Met:50Cys) and subdivided to receive either IP LPS or saline injections. LPS significantly increased total plasma Cys, homocysteine (Hcy) and glutathione (GSH) 240 min post-IP injection in rats fed a 50Met:50Cys ratio compared to other treatments. The TNF-α area under the curve for LPS-treated rats consuming a dietary 50Met:50Cys ratio was significantly higher (P < .004) compared to those consuming a dietary 100Met:0Cys ratio. A significant increase in the percentage of leukocytes that were neutrophils was observed in rats injected with LPS when compared to saline with no effect of diet. These results demonstrate that an alteration of the dietary Met:Cys ratio did not attenuate the inflammatory response to an IP injection of LPS in Wistar rats; however, a diet with a balanced Met:Cys ratio increased concentrations of Cys and GSH which may result in a more rapid response to an LPS challenge.

Keywords: Cysteine; Inflammation; LPS; Methionine; SAA ratio.