EFFECT OF DIETARY INDUCED OXIDATIVE STRESS ON INTESTINAL PHYSIOLOGY AND THE DEVELOPMENT OF MUCOSAL IMMUNITY TO ENTERIC PATHOGENS
Location: Diet, Genomics and Immunology Lab
Title: Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function
| Scanlan, Bradford - WALTER REED ARMY MED.CTR |
| Tuft, Blaine - WALTER REED ARMY MED CTR |
| Elfrey, Justin - U OF MD, SCHOOL OF MED. B |
| Zhao, Aiping - U OF MD SCHOOL OF MED BAL |
| Morimoto, Motoko - U OF MD SCHOOL OF MED-BAL |
| Chmielinska, J - GEO. WASH UMC, WASH.,DC |
| Tejero-Taldo, M - GEO. WASH UMC, WASH.,DC |
| Weglicki, William - GEO. WASH UMC, WASH.,DC |
| Shea-Donohue, Terez - U OF MD,SCHOOL OF MED,BAL |
Submitted to: Molecular and Cellular Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 2007
Publication Date: July 27, 2007
Citation: Scanlan, B.J., Tuft, B., Elfrey, J.E., Smith, A., Zhao, A., Morimoto, M., Chmielinska, J.J., Tejero-Taldo, M.I., Mak, I.T., Weglicki, W.B., and Shea-Donohue, T. 2007. Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function. Molecular and Cellular Biochemistry. Jul27;[Epub ahead of print].
Interpretive Summary: Magnesium deficiency can increase the amount of inflammation in the body. Ischemia, or lack of oxygen, is a common occurrence anytime blood flow to an organ or tissue is blocked, and when blood flow (and oxygen) is returned (called reperfusion) to the organ or tissue, damage can result. The aim of this study was to determine the effect of magnesium deficiency on the response to ischemia reperfusion. Rats were placed on control or magnesium deficient diets for 1 or 3 weeks and then the blood flow to the intestine was stopped for 30 minutes and then restored in half of the rats. Magnesium deficiency further increases inflammation in the intestine resulting from ischemia reperfusion. Increased inflammation was seen in the magnesium deficient rat that was associated with changes in expression of specific genes in the intestine. Giving the deficient rats supplemental magnesium did not change the effects of the deficiency alone, but reduced the inflammatory responses to ischemia and reperfusion. These studies are important to acute care practitioners. Future studies will examine the role of diets rich in magnesium on inflammatory responses to trauma.
Magnesium-deficiency (MgD)induces a systemic pro-inflammatory state. The aim of this study was to determine the effect of MgD on the functional and molecular response to mesenteric ischemia reperfusion. Rats were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 weeks and then randomized to either sham operation or superior mesenteric artery occlusion for 10 (non-injurious) or 30 (injurious) minutes followed by a 1- or 4-hour reperfusion period. Infiltration of PMNs and mucosal injury were assessed in stained sections of the small intestine. Magnesium deficiency alone induced a significant increase in PMN infiltration and exaggerated the PMN influx in responses to 10 and 30 minutes of ischemia and 1 or 4 hours of reperfusion. The increased inflammation was attenuated by acute magnesium repletion of deficient rats 24 hours before surgery. Mucosal injury was unaltered by magnesium deficiency. The increased sensitivity to oxidative stress in deficient rats was associated with alterations in the timing and duration of the expression of ICAM-1, COX-2, and NOS2. Immunohistochemistry showed increased ICAM-1 expression in submucosal blood vessels in magnesium deficient rats. Intestinal ischemia induced vascular macromolecular leak in the small intestine and lung at 4 hours of reperfusion. Magnesium deficiency alone induced vascular macromolecular leak in the small intestine and lung, which was attributed, in part, to reduced expression of constitutive NOS3. Acute magnesium repletion of deficient rats did not alter the effects of deficiency alone, but blunted the molecular and functional responses to mesenteric ischemia and reperfusion.