The role of l-arginine-nitric oxide pathway in bacterial translocation

Abstract

This study investigated the nitric oxide (NO) role as a mediator of arginine on bacterial translocation (BT) and gut damage in mice after intestinal obstruction (IO). The effects of pretreatment with arginine with or without NO inhibition on the systemic and local immunological response were also assessed. Mice were categorized into four groups. Group ARG received chow containing 2 % arginine, while group ARG + L-NAME received the same diet plus L-NAME (N-nitro-L-arginine methyl ester) by gavage. The IO and Sham groups were fed standard chow. After 7 days, animals were gavaged with radiolabeled Escherichia coli, anesthetized and subjected to IO, except the Sham group. Animals were euthanized after 18 h, and BT was evaluated in the mesenteric lymph nodes, blood, liver, spleen and lungs. In another experiment, the intestinal injury was assessed regarding intestinal permeability and ileum histological analyses. Intestinal secretory immunoglobulin A (sIgA) levels, serum IFN-γ and IL-10 cytokines were assessed. Arginine reduced BT, but NO inhibition enhanced BT compared with the ARG group (p < 0.05). Intestinal permeability in the ARG and ARG + L-NAME groups was similar but decreased when compared with the IO group (p < 0.05). Histological preservation was observed. Arginine treatment increased IL-10 and sIgA levels when compared with the Sham and IO groups (p < 0.05). The cytokines and sIgA concentrations were similar in the ARG + L-NAME and Sham groups. Arginine appeared to reduce BT and its effects on the modulation of cytokines and secretory IgA in mice after IO are mediated by NO production.

Arginine Supplementation Induces Arginase Activity and Inhibits TNF‐α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction

“…However, the ratio of TNF‐α/IL‐10 was significantly lower in the WT arginine‐supplemented animals. These results are similar to findings from other in vitro and in vivo studies illustrating the immunomodulatory role of arginine 7 , 22 , 23 . A study also conducted by our group 24 showed that supplementation of citrulline, an amino acid precursor to arginine, maintained the levels of IL‐10 and reduced serum IFN‐γ levels in a similar animal model of IO.…”

“…On the other hand, in the Arg WT group, the cell media concentration of TNF‐α was significantly reduced, and this may be related to the NO derivative of arginine, which seems to suppress the production of proinflammatory cytokines by macrophages in the spleen. This may explain our previous results on the positive impact of arginine supplementation on bacterial translocation and intestinal permeability, 4 ‐ 7 since continuous production of proinflammatory cytokines, such as TNF‐α may be more deleterious than beneficial during acute stress conditions 19 , 20 . Corroborating these data, Eun et al 20 evaluated the immunomodulatory effect of NO and observed that NO synthesis reduced the synthesis of the proinflammatory cytokines IL‐2 and IFN‐γ in cultured splenocytes.…”

“…In previous studies from our group, arginine positively affected bacterial translocation, intestinal permeability, and plasma cytokine production in an acute intestinal obstruction (IO) murine model 4 . ‐ 7 However, the exact mechanisms by which arginine exerts its role in these phenomena are yet to be determined.…”

Pretreatment and Treatment With L‐Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis

“…Studies have demonstrated that arginine supplementation improves various clinical parameters, 6 , 10 increases claudin‐1 expression, 10 and decreases colonic permeability and inflammatory cell infiltration 6 in experimental models of colitis. Previous results obtained by our research group have shown that arginine protects the intestinal mucosa, reducing intestinal permeability and bacterial translocation in experimental intestinal obstruction models 11 ‐ 14 as well as in a mouse model of physical exercise under heat stress 15 …”

Intestinal Mucositis Induced by Chemotherapy: an Overview

“…This fourth phase is characterized by integrity loss of mucosal and tissue morphological changes [7][8][9]. Reduction of the villus' height in humans [16] and animals [11] were observed after chemotherapy treatment. Due to epithelium ulceration the intestinal barrier becomes weak, which could lead to BT increasing the risk of bacteremia and sepsis [7][8][9].…”