Diet-induced antisecretory factor prevents intracranial hypertension in a dosage-dependent manner

Abstract

Intake of specially processed cereal (SPC) stimulates endogenous antisecretory factor (AF) activity, and SPC intake has proven to be beneficial for a number of clinical conditions. The aim of the present study was to investigate the dosage relationship between SPC intake and plasma AF activity and to further correlate achieved AF levels to a biological effect. SPC was fed to rats in concentrations of 5, 10 or 15 % for 2 weeks. A further group was fed 5 % SPC for 4 weeks. AF activity and the complement factors C3c and factor H were analysed in plasma after the feeding period. Groups of rats fed the various SPC concentrations were subjected to a standardised freezing brain injury, known to induce increases in intracranial pressure (ICP). The AF activity in plasma increased after intake of SPC, in a dosage-and time-dependent manner. The complement factors C3c and factor H increased in a time-dependent manner. Measurements of ICP in animals fed with SPC prior to the brain injury showed that the ICP was significantly lower, compared with that of injured rats fed with a standard feed, and that the change was dose and time dependent. AF activity increases, in a dosage-and time-dependent manner, after intake of SPC. The inverse relationship between ICP after a head injury and the percentage of SPC in the feed indicate that the protective effect is, to a large extent, due to AF.Key words: Antisecretory factor activation: Complement factors: Intracranial pressure: ELISA: Inflammation Antisecretory factor (AF), also named S5a, is a 43 kDa ubiquitously expressed protein originally identified through its capacity to inhibit intestinal hypersecretion (1) . Further studies have shown that AF is also a potent anti-inflammatory agent (2 -6) . In the plasma of healthy individuals, the major part of AF is present in an inactive form (7) . AF is activated through intestinal exposure to bacterial toxins or through the intake of specific food components, e.g. in the form of specially processed cereals (SPC) (7 -9) . Clinical studies have shown that a diet-induced increase in AF activity is beneficial for a number of diseases in which inflammation and/or secretory disturbances are parts of the pathophysiology (6,8,9) .The mechanisms through which SPC activate AF are currently unknown, although exposure of the intestinal mucosa to SPC, in certain aspects, may be assumed to mimic that of intestinal exposure to bacterial toxins, i.e. by inducing an inflammatory response. Such a response could be a first step in the activation process. In a previous study, proteomics was used to study the differences in protein expression in the livers of rats fed an SPC feed and rats fed a standard feed (10) . A selective increase in the expression of glutathione-S-transferase m in the livers of rats fed the SPC feed was observed. Glutathione-S-transferase m does not appear to be involved in AF activation, and the increased expression is probably an unrelated effect of the SPC feed.In a recent study, in which rats were exposed to blast injury t...

Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging

“…In general, the clinical results obtained from research on using SPC-treatment for various diseases indicate that SPC-intake also might influence nervous tissues directly. Thus, intracranial pressure in the brain induced by an experimental head trauma was significantly decreased after four weeks of SPC intake in rats6.…”

“…An endogenous increase of AF counteracts the clinical intestinal symptoms in patients suffering from inflammatory bowel disease5 and is also known to provide protection against raised intracranial pressure induced by experimental head trauma6. The “active site” of AF was found to be 8 amino acids located in the N-terminal part of this protein and this 8-amino acid peptide is responsible for regulating inflammation and secretion7.…”

“…A four-week dietary intake of SPC in rats has been demonstrated to counteract an increase of intracranial pressure in response to an experimental head trauma6. It has also been demonstrated that AF in the central nervous system (CNS) interacts with subcellular structures3536.…”

Faecal analysis and plasma complement factor 3c levels at admission for an acute attack of ulcerative colitis are predictive of the need for colectomy

“…The patients recorded their daily number of stools and weight of each stool (using a removable toilet seat faecal collector unit and an electronic scale) separately during the initial 24 h. The blood samples for analysis of cytokines, C3c and AF were collected in citrate tubes at admission, immediately centrifuged and stored at -701C for later measurement. The level of C3c in the affinity-purified human plasma samples was determined by an enzyme-linked immunosorbent assay (ELISA) method using rabbit anti-C3c polyclonal antibody (Dako, Glostrup, Denmark) as the detecting antibody [19]. A second antibody, of goat anti-rabbit immunoglobulin G (IgG)-alkaline phosphatase conjugate (Jackson ImmunoResearch Europe Ltd, Suffolk, UK), was then applied, followed by reading absorbance at 405 nm to reveal the bound enzyme.…”

“…Complement factor C3c, one of the fragments that result from the proteolysis of C3b, is a biologically inactive product, which has been suggested as a possible inflammatory marker [18]. Furthermore, plasma levels of C3c have been shown to correlate with diet-induced antisecretory factor (AF) formation in an animal model of inflammation [19].…”