Dietary isoflavones suppress endotoxin-induced inflammatory reaction in liver and intestine
Introduction
Inflammation is an essential biological defense yet excess immune response can lead to tissue damages [1]. Consistent with this, anti-inflammatory agents have been found to have the cancer prevention activity [1]. Dietary isoflavones were implied in cancer prevention [2], [3] but their in vivo effects on immune response remain to be clarified. Intraperitoneal injected genistein was shown to protect rats from the endotoxin-induced organ failure [4]. Subcutaneously injected or oral intake of isoflavone genistein was found to decrease thymic size and humoral immunity in castrated or ovariectomized mice [5]. On the other hand, genistein by gavage was found to enhance host resistance to intravenously-injected tumor cells [6]. Since the main route of isoflavone exposure in human population is through soybean ingestion, we determined the immune-modulating effect of dietary soy isoflavones in normal mice here.
Intestine is potentially a target organ for the chemoprevention activity of isoflavones based on epidemiological studies [2]. Since anti-inflammatory agents have colon cancer prevention activity [1], [7], we are interested in the intestinal immune response in soy isoflavones-fed mice. In addition, orally-ingested isoflavones can be transported across the intestinal epithelium [8], [9], [10], [11] although their systemic availability is limited [12]. Liver, because of its proximity to the intestine in blood supply, could also benefit from the dietary component. Indeed, inflammatory responses in intestine and liver have been described before [13], [14], [15] and were shown to be modulated by dietary component [13]. In this paper, we compared the endotoxin-induced inflammation reaction in these two organs in mice that were fed diet with or without isoflavones. In addition, the potential mechanisms of immune suppression by genistein were examined using cultured cells.
Section snippets
Animal studies
Male 9 weeks-old C57/BL6 mice were used for the study. After acclimation to the isoflavones-free AIN-93M diet (C diet), they were randomly assigned to C diet or AIN-93M supplemented with 0.3% (3 g/kg) Novasoy® (Archer Daniel Midland Co., Decatur, IL). (ISF diet). The composition of Novasoy® was determined by LC-PDA and LC-MS analysis [16], [17] (Table 1). The mice were housed individually under 12-h light/dark cycle (10 PM/10 AM). Food intake and body weight were monitored twice every week.
Effect of isoflavone diet on body weight, food intake and tissue glutathione levels
The body weight of four groups of mice, control (C) diet with saline injection, isoflavone (ISF) diet with saline injection, C diet with LPS injection, and ISF diet with LPS injection was 29.5±2.9, 29.0±3.0, 28.1±3.6, and 29.6±2.8 g, respectively (mean±SD, N=8–9 in each group). The daily food intake of these four groups of mice was 3.5±0.2, 3.4±0.4, 3.5±0.3, and 3.5±0.3 g, respectively (mean±SD, N=8–9 in each group). There were no differences among groups in body weight or food intake.
Glutathione
Discussion
We demonstrated here the ability of a diet containing soy-derived isoflavones to modulate the tissue response to endotoxin challenge. Mice given soy isoflavone diet did not exhibit LPS-induced hepatic glutathione loss (Table 2) and had less LPS-induced hepatic and intestinal gene induction (Fig. 1). Previously, a diet with a similar concentration of soy isoflavones was found ineffective in increasing cardiac graft survival although intraperitoneal genistein has the immunosuppressive property
Acknowledgements
We thank James Boyer, Wan-Jung Tsai and Di Tan for technical support. This study was supported in part by NIH grant DK33886 (to H.B.) and DK54728 (to S.-M. K.)
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