metallothionein and Diarrhea

Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

Topics: Animals; Diarrhea; Diet; Gene Expression Regulation, Enzymologic; Interleukin-1; Intestinal Mucosa; Intestines; Male; Metallothionein; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Zinc

The effect of free fatty acids on zinc absorption was studied in a rat model of chronic osmotic diarrhea induced with magnesium citrate and phenolphthalein. In vivo rates of zinc removal from the lumen and analysis of tissue for zinc uptake and metallothionein alterations were monitored. One mmol/L stearate enhanced zinc absorption in rats with or without diarrhea, from 207 +/- 22 and 353 +/- 13 pmol/min x cm to 676 +/- 34 and 610 +/- 26 pmol/min x cm, respectively. Palmitate was only effective in normal rats. Zinc absorption inversely correlated with mucosal zinc content in the perfused intestinal segments, in both type of rats. Hepatic metallothionein was enhanced by zinc and even more by oleate plus zinc in both groups; kidney metallothionein in animals with diarrhea was normalized by either oleate or zinc. The data support previous reports on the effect of long-chain fatty acids on the enhancement of zinc absorption: saturation and a longer chain appear to be positive factors. A membrane modification role of long-chain fatty acids could have nutritional implications in the formulation of special diets.

Topics: Animals; Biological Transport; Diarrhea; Disease Models, Animal; Fatty Acids; Intestinal Absorption; Kidney; Liver; Male; Metallothionein; Osmosis; Perfusion; Rats; Rats, Wistar; Sodium; Zinc

The effect of preinduction of metallothionein (MT) by bismuth (Bi) compounds on the toxic side effects and antitumor activity of adriamycin (ADR) was investigated in mice. Preinduction of MT by oral administration of bismuth subnitrate (BSN) significantly decreased the lethal toxicity, cardiotoxicity and bone marrow toxicity observed with a single subcutaneous injection of ADR. A significant increase in the concentration of cardiac MT was observed in mice treated with BSN. The MT level in the heart was significantly correlated with the protective effect of BSN against the cardiotoxicity of ADR. In tumor-bearing mice, pretreatment with BSN did not affect the antitumor activity of ADR, although its cardiotoxicity was significantly depressed. The ability of BSN to reduce specifically the toxicity of ADR may be ascribed to the fact that Bi induces MT in the target tissue of ADR toxicity but not in a tumor. The protective effect of MT against the toxicity of ADR, which is believed to act as an anticancer agent by generating active oxygen, can be assumed to be due to its ability to scavenge free radicals or inhibit their formation.

Topics: Animals; Bismuth; Bone Marrow; Carcinoma, Ehrlich Tumor; Diarrhea; Doxorubicin; Drug Administration Schedule; Heart; Male; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Inbred ICR