Dietary magnesium depletion does not promote oxidative stress but targets apical cells within the mouse caput...

It is well documented that a dietary deficiency in magnesium can induce oxidative stress and an inflammatory response in animal models. In our study, we have investigated these responses in the mouse epididymis after mice had been fed a magnesium-deficient diet for a 2-week duration. The extracellular and intracellular concentrations of magnesium where shown to be depleted on this diet. This was followed, however, only in the liver of the Mg-deficient animals, by an increase in both alpha 2-macroglobulin (alpha-2m), an acute phase marker, and interleukin-6 transcripts suggesting that an inflammatory response had been initiated. These changes were correlated with a decrease in circulating neutrophils. To address the question of whether or not peroxidation was induced in mouse epididymis following hypomagnesia, we have monitored the level of endogenous peroxidation, their ability to respond to induced peroxidation as well as the expression and activity of the enzymatic glutathione peroxidase (GPX) antioxidant family. To evaluate if the epididymis had evolved specific protections against peroxidation, other organs such as the liver and the kidney were monitored in parallel. We detected no evidence for increased peroxidation in any of the mouse organs tested. However, GPX activity was found to be significantly lower in the liver and the kidney of Mg-deficient animals while it was unchanged in the epididymides of the same animals during the deficiency. Histological analysis of the epididymis showed no major difference in the overall cytological aspect of the organ. Segment 2 of the caput, however presented a significant increase in the number of apically located cells or blebbing cells. Immunohistochemical analysis proved that these cells were epididymal apical cells and not infiltrated leukocytes. These observations suggested that the mouse caput epididymidis segment 2 specifically responded to Mg deficiency via the apical cells. Finally, a comparative analysis of stress response genes was conducted in control and magnesium-deficient caput epididymidis samples. It brought forward some genes that might be involved in the peculiar response of the caput epithelium following hypomagnesia.