Jeanine Fontaine

Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats

Trace elements such as zinc, copper and selenium are involved in the pathogenesis of inflammatory diseases. In order to obtain more information about the overall movements of these minerals during the evolution of an experimental chronic inflammatory process, trace element levels were determined in five body compartments of the rat at several time intervals after induction of adjuvant arthritis. Rapid and significant changes in plasma zinc and copper levels and in liver zinc levels were observed. These modifications occurred as early as those in biochemical parameters of inflammation such as serum fibrinogen and ceruloplasmin, and preceded the appearance of any clinical symptom of the disease. Inverse correlations were found between plasma zinc levels and these two biochemical indices. Other modifications in trace element levels were observed two weeks after disease induction, the most important being a considerable increase in liver copper levels. Although food intake of affected animals decreased with the progression of the disease, there was no evidence of depletion in zinc and copper levels over the study period. A redistribution of body zinc between different biological compartments (mainly plasma and liver) occurred simultaneously with an accumulation of copper in several organs. The decreasing selenium status of animals was not clearly related to the inflammatory process.

Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation.

SummaryStarting from the experimental design of the established ‘Zinc Tolerance Tests’, the absorption and distribution of the essential trace element zinc in humans was investigated in 10 subjects by performing a pharmacokinetic study of the serum zinc profile after oral administration of a pharmacological dose of the metal, i.e. 0.69 mmol (45 mg) zinc as ZnSO4.7 H2O. The adopted experimental conditions include frequent measurements of serum concentrations, a total investigation time of 8 h after ingestion, and a correction of basal zinc levels taking into account the circadian variation. Rebound effects were evidenced in the time versus concentration curves showing a regular recycling of the element in the digestive tract. Estimation of the parameters by an original method allowed us to calculate the characteristics of the cycles. The first one occurred after 1.4 h, before the time needed for appearance of the maximum concentration which was around 2.3 h, and exhibited mean reabsorption of 70% of administered dose. The subsequent ones, maximum 5 during the investigation period, appeared at regular intervals of approximately 1.2 h, with a decrease in the quantity reabsorbed. These observations are consistent with the previously reported endogenous secretion of zinc, a physiological mechanism contributing to zinc homeostasis.

Effects of acute prednisolone administration on plasma and liver copper in rats with adjuvant arthritis

Several studies in animals and humans have shown that copper metabolism could be affected by inflammation or by corticosteroids. The relative importance of these two factors, often imbedded in clinical practice, was assessed by investigating the effects of acute prednisolone administration (30 mg/kg, ip) on healthy and adjuvant arthritis rats. Plasma copper levels were significantly higher in arthritic rats compared to healthy animals, whereas there was a slight, but nonsignificant increase in liver copper. Acute prednisolone administration in healthy rats resulted in a significant increase in plasma copper (10–15%) as early as 4 h after corticosteroid administration, which was maintained for 12 h. In arthritic rats, the response was much higher (25–40%), but somewhat delayed and shorter. Liver copper was not clearly modified by prednisolone treatment in both groups. This time-controlled study showed that acute prednisolone administration increased plasma copper in both healthy and arthritic rats, but in different ways, indicating that inflammation and corticosteroids may act synergistically.