Idiorrhythmic zinc dose-rate induction of intestinal metallothionein in rats depends upon their nutritional zinc status†

The idiorrhythmic dose-rate feeding experimental model was used to study the induction of intestinal metallothionein (iMT) by zinc (Zn) in the gastrointestinal (GIT) mucosa of young growing male rats relative to their nutritional Zn status. The idiorrhythmic approach requires that the average dietary Zn concentration, referred to as modulo (M), is kept constant across different groups over the whole experimental epoch (E). This is done by adjusting the Zn concentration of the supplemented diet to compensate for the reduction in the number of days on which this diet is fed, the latter being spread evenly over the whole experiment. Idiorrhythms (I) involve offering the diet with n times the overall Zn concentration (M) only every nth day with a Zn-deficient diet offered on other days. We studied three modulos (low-Zn, M3; adequate-Zn, M12; and high-Zn, M48), each M having 8 analogous idiorrhythms (I = Mx/1 to 8Mx/8); every I was fed over a 48-d idiorrhythmic E. Over the wide range of peak doses of dietary Zn (3–384 mg Zn/kg diet), the higher the modulo, the greater the capacity for iMT to be induced (M3 < M12 < M48; P < 0.05). Also, the ability of Zn to induce iMT increased proportionally with the progression of the idiorrhythms from I = Mx/1 to 8Mx/8 (P < 0.001). When rats were fed M3, less Zn was required to induce iMT than when they were fed M12 or M48. Thus, within the M and E limits of this study, the better the nutritional Zn status of the animal, the more Zn is required to induce iMT and vice versa. The fact that iMT was increased means that the amount of available Zn was not proportional with the actual steady state of its metabolism. This indicates that for any Zn supplementation program to be effective, it should progress gradually from a lower to a higher Zn dose relative to the given nutritional Zn status.