Hepcidin in acute iron toxicity.

BACKGROUND: Hepcidin regulates extracellular iron concentration by inhibiting iron release from macrophages and preventing iron absorption in the intestine. Our objective was to evaluate the expression of hepcidin in the liver in acute iron poisoning in a rat model. METHODS: Male Wistar rats were assigned to group 1, who received 750 mg/kg elemental iron (LD(50)) by gavage, and group 2 (control), who received distilled water. Iron concentrations and liver transaminases were measured in the serum. Hepcidin messenger RNA levels were measured in the liver. RESULTS: Mean serum iron levels, aspartate aminotransferase, alanine aminotransferase, and uric acid were significantly higher in group 1 compared to group 2 (P < .0001, P = .01, P < .0001, and P = 0.0001, respectively). Hepcidin messenger RNA levels in the liver were significantly higher in the study group (P = .005). CONCLUSIONS: In acute iron intoxication, hepcidin expression in the liver significantly increased. Further studies are needed to determine whether hepcidin levels correlate with the severity of the intoxication.

Depletion of glutathione system enzymes of the liver and erythrocytes in a rat model of acute iron poisoning.

ABSTRACT The proposed mechanism of iron-induced hepatotoxicity is free radical formation. It was hypothesized that the glutathione system of the liver and erythrocytes will be affected by acute iron poisoning. Male Wistar rats, 6-8 weeks of age, were assigned to one of three groups. Group I received distilled water, group II received 400 mg/kg elemental iron, and group III received 750 mg/kg elemental iron. All groups were gavage fed. Iron concentration, glutathione, and glutathione system enzymes were then measured in the liver and erythrocytes. The hepatic level of reduced glutathione (GSH) was significantly lower in groups II (3.1 +/- 4.6 mumol/mg protein) and III (4.7 +/- 4.6 mumol/mg protein) in comparison with group I (11.5 +/- 6.2 mumol/mg protein) (p < 0.001). Hepatic levels of glutathione S-transferase (GST) were higher and glutathione peroxidase (GPX) levels were lower in group III compared to groups II and I (p < 0.001 and p < 0.001). Compared to group I, glutathione reductase (GR) was lower in groups II and III (p < 0.001). There was no correlation between GSH, oxidized glutathione (GSSG), GST, GR, and GPX levels in the erythrocytes and in the liver (p = 0.41, p = 0.48, p = 0.49, p = 0.53, p = 01.4, and p = 0.84, respectively). In conclusion, acute iron intoxication in rats is associated with depletion of reduced glutathione in the liver.