Endogenous metal binding proteins in relation to the differences in absorption and distribution of mercury in newborn and adult rats

Abstract

Abstract. Both in the ilatestinal copper complex and hepatic zinc-thionein of the newborn rat provide immediately available, high-affinity binding sites for Hg 2+. Retention of orally administered Hg 2+ in the gastrointestinal tract is much greater in the 5-day old rat than in the weanling and accounts for most (70-90%) of the body burden at 18 h. At a dose level of 790 ~tg Hg2+/kg body weight, 41% of the Hg 2 § retained in the gastrointestinal tract of the newborn animal is located in the soluble fraction of the mucosa and 48% of this is bound by the copper-complex. This complex, therefore, seems to limit the transfer of Hg 2+ from the mucosa to the serosa. It does not appear, however, to be a primary acceptor of Hg 2+ in the neonatal intestine since, after administration of 100 ~tg Hg2+/kg body weight, its binding of Hg 2+ is less (33% of the soluble Hg 2 § than that (67% of the soluble Hg 2 § of the high molecular weight protein fraction.At 18 h after the intraperitoneal administration of Hg 2+ (790 ~tg Hg2+/kg body weight), whole body retention is greater in the adult (80% of the dose) than in the suckling or weanling animal (63-68% of the dose). In the suckling animal the inter-and intra-organ distributions of the retained Hg 2+ also differ from those in the weanling and/or adult rat. Thus the ratio of the renal:hepatic Hg 2+ contents, after either intragastric or intraperitoneal doses of Hg 2+, increases with age. Also most (approximately 90%) of the Hg 2+ retained in the liver of the newborn animal after an intragastric dose is bound by the metallothionein whereas, in the adult liver, only 4% of the total Hg 2 § is in this form. The presence of the metallothionein, however, is not the cause of the increased Hg > uptake in the former, since induction of hepatic zinc-thionein in the adult by pretreatment with Zn 2+ does not affect the distribution of Hg 2 § between the liver and kidneys.These findings are discussed in relation to the known differences in intestinal absorption and tissue distribution of Cd 2+ and Hg 2+ in newborn

Effect of Age and Diet on Renal Cadmium Retention in Rats

“…The retention in the liver was slightly lower in sucklings than in older rats. This supports the conclusions made by several authors that the higher liver metallothionein concentration (18,19) does not influence cadmium distribution (15,20,21). The higher brain retention found in sucklings is in agreement with several previously published results (11,22).…”

“…Immaturity obviously influences uptake from blood to organs as well as elimination and perhaps age-related differences in the binding affinities and/or content of metal carrier proteins. These and other possibilities are discussed in detail elsewhere (21,(37)(38)(39).…”

Lactating and nonlactating rats differ to renal toxicity induced by mercuric chloride: the preventive effect of zinc chloride

“…28,36,[54][55][56][57] In line with this, it was previously demonstrated that preexposure to ZnCl 2 prevents the renal damage and the inhibitory effect in the renal δ-ALA-D activity induced by HgCl 2 in young rats concomitantly to the increase of MT levels. 28,34 Because the sensitivity of developing animals to various compounds (including metals) may differ from that observed in adults, [19][20][21][22] we also evaluated the effects of metals in pups via maternal milk. The transport of inorganic mercury into milk was previously demonstrated in rats by Sundberg et al 58 and in guinea pigs by Yoshida et al 59 Indeed, Sundberg et al 58 demonstrated that mercury concentration in milk is linearly correlated to the levels in the kidney of suckling pups after exposure to mercury via milk.…”

“…The sensitivity of developing animals to various compounds (including metals) may differ from that observed in adults, [19][20][21][22] making the study of metal effects on developing organisms important. In fact, young animals, mainly during the first days after birth, seem to be more sensitive than adults to toxic agents.…”

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

“…An ionized compound will not enter the CNS as readily as a compound that is not ionized, in which case it will enter the brain at a rate proportional to its lipid:water partition coefficient (171). For example, methyl mercury enters the brain much more readily than inorganic mercury (110,172).…”