metallothionein and Pre-Eclampsia

Cadmium-metallothionein, mobilized from the liver, might be the toxic serum factor associated with pre-eclampsia. We base this on four documented concepts. First, during pregnancy, maternal physiology adjusts to assure the fetus of the proper amounts of nutrients necessary for growth. Our focus is on zinc and progesterone. Second, because zinc and cadmium are similar, they compete for binding sites. Our focus is on the storage protein metallothionein. Third, the manifestations of cadmium toxicity closely mimic the manifestations of toxemia (i.e. hypertension, proteinuria, edema). Our focus is on cadmium-induced endovasculitis. Fourth is the concept that metallothionein-bound cadmium can be mobilized from the liver into the serum during pregnancy as it follows the mobilization of metallothionein-bound zinc. Our focus is on the extreme toxicity of extracellular cadmium-metallothionein. We correlate these four concepts into a rational theory on the etiology of toxemia, and we suggest a method of proof.

Topics: Cadmium; Female; Humans; Liver; Metallothionein; Pre-Eclampsia; Pregnancy

Laboratory animals have a unique sensitivity to cadmium toxicity in late pregnancy. This acute toxicity is not seen in non-pregnant, early pregnant, or lactating animals. Furthermore, during late pregnancy, laboratory animals absorb and retain substantially more cadmium from their diets than they do in the non-pregnant state. Both of these observations parallel the fact that a fivefold late gestational drop of maternal metallothionein (a metal-binding protein believed to detoxify cadmium) has been demonstrated in pregnant animals. Additional factors such as nutritional status and age affect cadmium absorption. As we have discussed previously, cadmium toxicity and toxemia of pregnancy have many common features including hypertension, proteinuria, edema, vasospasm and endovasculitis. Because of the above, we propose that cadmium plays a role in the etiology of toxemia.

Topics: Animals; Cadmium; Female; Humans; Hypertension; Maternal-Fetal Exchange; Metallothionein; Pre-Eclampsia; Pregnancy; Rats

Cadmium, a toxic heavy metal, has been incriminated in the etiology of essential hypertension. Zinc, an essential micronutrient necessary for growth, competes with cadmium for binding sites in biochemical processes; zinc deficiency states (i.e. pregnancy and low protein diet) might expose an individual to increased risk of cadmium toxicity. The increased sensitivity to cadmium during pregnancy could also be related to the effect of progesterone on zinc and cadmium metabolism through the actions of metallothionein (MT). MT is a low molecular weight protein believed to function in cadmium detoxification. Several studies in lab animals have documented a late gestation drop of maternal MT levels. This was thought to be due to rising progesterone levels. If there is also a late gestation drop in human maternal MT, then the propensity toward maternal cadmium toxicity would be enhanced. Therefore, we propose that when a zinc deficient woman becomes pregnant and is exposed to both the nutritional demands of the fetus and to the influence of progesterone, she will be likely to develop the manifestations of cadmium toxicity (i.e. hypertension, proteinuria, edema, etc.).

Topics: Animals; Cadmium; Female; Humans; Hypertension; Metallothionein; Models, Biological; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Progesterone; Zinc