Effect of lead on Na+,K+ ATPase activity in the developing brain of intra-uterine growth-retarded rats

Abstract

Lead (Pb) intoxication in developing mammals, including humans, produces serious brain damage. In addition, it is known that nutritional status influences the susceptibility to Pb toxicity. We developed an in utero undernutrition model based on restriction of blood supply to fetuses on d 17 of pregnancy (IUGR rats). The aim of this study was to investigate in vitro the possible effect of Pb on Na+, K+ATPase activity in the brain of developing IUGR and control rats from 6 to 60 d after birth. In addition, we measured the stimulation of Na+, K+ATPase by the monoamines noradrenaline and serotonin. Our results show that: The neurotoxic effect of Pb is an age-related phenomenon. Both IUGR and control rats were more sensitive to Pb in the first week of life. In adults, Pb had a weak inhibitory potency; the delayed matured brain in IUGR animals seemed less sensitive to Pb when compared to age-paired control rats; in the IUGR group, at 15 and 22 d, low doses of Pb had a stimulatory effect on Na+, K+ATPase instead of an inhibitory effect; noradrenaline and serotonin stimulated Na+, K+ATPase activity to an equivalent extent, but this was greater in IUGR than control rats; and at low Pb concentrations, the studied monoamines reversed Pb-induced inhibition.

Inhibition by Lead of Production and Secretion of Transthyretin in the Choroid Plexus: Its Relation to Thyroxine Transport at Blood–CSF Barrier

“…We recently observed that Pb potently inhibited the activity of mitochondrial complex-I (NADH-ubiquinone reductase), the enzyme that is critical to the energy production in mitochondrial respiratory chain (unpublished data). Others have reported that Pb inhibits cellular ATPases (Chanez et al, 1986;Rajanna et al, 1991). In addition, we have demonstrated that Pb exposure promotes the translocation of protein kinase C (PKC) from the cytosol to membrane in the choroid plexus .…”

Impaired energy‐dependent processes underlie acute lead neuropathy

“…Axonal excitability studies were undertaken during the acute phase and in convalescence to assess whether lead exerts its neurotoxic effects through dysfunction of axonal biophysical properties, a hypothesis that has received support from in vitro studies 5. The patient gave informed consent to the procedures, which were approved by institutional ethics committees.…”