Effect of Iron Succinyl-Protein Complexes on Gastrointestinal Motility in the Fasting Dog

Abstract

Studying the gastrointestinal motor effects of iron compounds may help to elucidate the mechanism originating the gastrointestinal side effects frequently reported during martial therapy. The aims of the present study were: (1) to examine the gastrointestinal motor effects of ferrous sulfate (reference compound) and (2) to compare its effects with those of two iron succinyl-protein complexes (ITF 1096 and ITF 282, an iron-albumin and iron-casein complex, respectively). In 6 fasting, conscious dogs, fitted with 8 bipolar electrodes and 3 strain-gauge force transducers along the gastrointestinal tract, gastrointestinal motor activity was recorded. Ferrous sulfate and iron succinyl-protein complexes were administered by an orogastric tube at two dose levels: the lower and higher dose levels were approximately equivalent to 10 and 30 mg/kg as Fe, respectively. In control experiments, 154 mM NaCl, ITF 211 (succinylated albumin) and ITF 297 (succinylated casein) were used. Administration of 154 mM NaCl did not affect gastrointestinal motility nor did it disrupt migrating motor complex (MMC) cycling. ITF 1096 and ITF 282, only at the higher dose, lengthened the MMC period and increased intestinal, but not gastric spike activity. The effects of ITF 211 and ITF 297 were similar to those of ITF 1096 and ITF 282. Ferrous sulfate, at the lower dose, lengthened the MMC period; the higher dose disrupted MMC cycling and induced intense, irregular spike bursts in the stomach and in the small bowel, accompanied, in 3 out of 6 dogs, by a prolonged tonic contraction of the upper small bowel. Four out of 6 dogs vomited after the higher dose of ferrous sulfate. No vomiting was observed with any of the other treatments. We conclude that ITF 1096 and ITF 282 have a markedly better gastrointestinal tolerability than ferrous sulfate.

Motility changes induced by intraluminal FeSO4 in guinea pig jejunum

“…Finally, the concentration of FeSO 4 used in this study in the guinea pig jejunum was based on approximations of the luminal concentration reached following various doses from previous studies investigating its physiological effects in other animal models and on measured iron levels in the human intestinal lumen . In dog, De Ponti et al .…”

“…Finally, the concentration of FeSO 4 used in this study in the guinea pig jejunum was based on approximations of the luminal concentration reached following various doses from previous studies investigating its physiological effects in other animal models and on measured iron levels in the human intestinal lumen . In dog, De Ponti et al . administered a dose of ~500 mg of FeSO 4 in 125 mL (50 mg/kg for a ~10 kg dog) via a gastric tube, which would yield a maximum concentration in the stomach of ~25 mM (5 mM elemental iron), but would be diluted by gastric juice before passing into the duodenum.…”

“…De Ponti et al 15 investigated the effects of iron supplements on intestinal motility. They found that orogastric administration of ferrous sulfate (FeSO 4 ) at concentrations similar to supplementation altered intestinal migrating motility complexes and caused prolonged tonic contractions in dog small intestine when compared with a saline infusion.…”

Edaphic and Phytochemical Factors as Predictors of Equine Grass Sickness Cases in the UK

“…Although it is commonly known that excess iron in the diet can cause constipation in humans (for example it is a common side-effect of iron supplementation routinely prescribed in pregnancy; Paesano et al, 2009), there have been surprisingly few studies specifically investigating the impact of iron on mammalian gastrointestinal motility (e.g., De Ponti et al, 1991; Nasu et al, 2001). The higher levels of heavy metals found in herbage from EGS sites may inhibit gastrointestinal motility.…”

Acute allergic reaction to an iron compound in a milk‐allergic patient

“…Conjugation of iron to proteins has proved a valid strategy to, at least partially, overcome these problems. The binding of iron to succinylated milk proteins, as casein or albumin, has been one of these strategies (1, 9), but the only one of such complexes commercially available is iron caseinsuccinylate.…”