Disaccharidase levels in normal epithelium of the small intestine of rats with iron-deficiency anemia

Abstract

Iron-deficiency anemia is the nutritional deficiency most frequently occurring throughout the world, which manifests as a complex systemic disease involving all cells, affecting enzyme activities and modifying protein synthesis. In view of these considerations, the objective of the present study was to determine the effects of irondeficiency anemia on disaccharidases and on the epithelial morphokinetics of the jejunal mucosa. Newly weaned male Wistar rats were divided into 4 groups of 10 animals each: C6w received a standard ration containing 36 mg elemental iron per kg ration for 6 weeks; E6w received an iron-poor ration (5-8 mg/kg ration) for 6 weeks; C10w received an iron-rich ration (36 mg/kg ration) for 10 weeks; E10w received an iron-poor ration for 6 weeks and then an iron-rich ration (36 mg/kg) for an additional 4 weeks. Jejunal fragments were used to measure disaccharidase content and to study cell proliferation. The following results were obtained: 1) a significant reduction (P<0.001) of animal weight, hemoglobin (Hb), serum iron and total iron-binding capacity (TIBC) in group E6w as compared to C6w; reversal of the alterations in Hb, serum iron and TIBC with iron repletion (E10w = C10w); animal weights continued to be significantly different in groups E10w and C10w. 2) Sucrase and maltase levels were unchanged; total and specific lactase levels were significantly lower in group E6w and this reduction was reversed by iron repletion (E10w = C10w).3) The cell proliferation parameters did not differ between groups. On the basis of these results, we conclude that lactase production was influenced by iron deficiency and that this fact was not related to changes in cell population and proliferation in the intestinal mucosa.

Decreased sucrase and lactase activity in iron deficiency is accompanied by reduced gene expression and upregulation of the transcriptional repressor PDX-1

“…In agreement with previous studies, it was observed that iron-deficient Wistar rats have significantly lower sucrase and lactase activities compared with their control littermates (2,4,5,9,16,20,31,38). This decreased activity cannot be attributable to changes in kinetic properties of the enzymes as evidenced by no significant differences in K m values, inferring that it is primarily due to reduced quantities of the enzyme present in the mucosa.…”

“…The enzymatic activity of each individual disaccharidase is influenced primarily by the dietary level of their corresponding substrate (2, 12), and, under normal conditions, this level of activity is controlled by the abundance of the mRNA encoding the proteins (12, 34). However, it has been shown on many occasions that dietary iron deficiency can cause a significant decrease in disaccharidase activity (2,4,5,9,16,20,31,38) and that this decrease is reversible by iron supplementation (9,20,38).…”

“…In addition, it has been shown that many other functions of the intestinal mucosa are adversely affected by iron deficiency, including a significant decrease in the secretory component (4, 5), a decrease in the specific activity of diamine oxidase (4, 5), and an apparent inability to manufacture membrane-bound high-molecular-weight glycoproteins (20). As such, most hypotheses explaining the mechanisms of the relationship between iron status and disaccharidase activity focus on an impaired ability to manufacture all brush border glycoproteins, either at the level of initial synthesis, posttranslational modification, or trafficking to the brush border membrane (4,5,9,20,38).…”

“…Most importantly, cell proliferation requires iron (21), yet intestinal morphology is rarely different from normal, even under severe iron deficiency (4,9,16,30). More specifically, the DNA synthesis rate of intestinal enterocytes is not affected by iron deficiency (4,27), nor is the proportion of mitotic cells in the mucosa (9).…”

Culture of human intestinal epithelial cell using the dissociating enzyme thermolysin and endothelin-3

“…The epithelium of the small intestine is continuously and rapidly renewed in a process involving cell generation and migration from the multi-potential stem cells, housed in specific "niches" within the crypts, to the extrusion of the terminally differentiated cells at the tips of the villi, within a period of 3-5 days (24). HIEC play a central role in absorptive and secretory functions, protecting the organisms from bacteria and toxins, providing an effective barrier against the complex antigenic load of intestinal contents (3,25).…”