Lead toxicity tissue

Free-radical-induced oxidation of low-density lipoprotein (LDL) may be another mechanism that leads to tissue injury. Following incubation with endothelial or smooth muscle cells, LDL oxidizes and becomes toxic to proliferating fibroblasts (Morel et al., 1983a). 

Areola 00, Williams-Johnson M, Jadhav AL. 1999. Relationship between lead accumulation in blood and soft tissues of rats subchronically exposed to low levels of lead. Toxic Substances Mechanisms 18 1-13. 

Hayashi M. 1983. Lead toxicity in the pregnant rat 11. Effects of low-level lead on delta-aminolevulinic acid dehydratase activity in maternal and fetal blood or tissue. Ind Health 21 127-135. 

No effect on food intake or growth. Blood and tissue lead levels elevated, but no overt signs of lead toxicity. Lead concentrations (controls vs. dosed birds) were 0.6 vs. 1.3 mg/kg FW in blood, <0.1 vs. 7 mg/kg DW in liver, and <0.1 vs. 30 mg/kg DW in kidney... 

Increased susceptibility of certain segments of the population, e.g., young children, may arise from increased tissue sensitivity, more complete absorption, altered distribution, or less developed or impaired defense mechanisms. The increased sensitivity of the child to lead toxicity is well documented (100, 101). In children, unlike the adult, renal tubular damage and encephalopathy are more common sequelae (76, 100). With arsenic exposure, children show significantly higher concentrations of the element in hair and urine than do adults (62). 

Correct answer == C. Ergotamine acts to counteract cerebral vasodilation that plays a rale in migraine headaches. Vasoconstriction leading to tissue ischemia is one of the toxic complications associated with an overdose of these drugs. The ergot aikaioids interact with adrenergic, dopaminergic, and serotonin receptors. They... 

Figure 16.2. Mechanisms of cellular toxicity. Tissues are comprised of cells, and each cell is defined by its cell membrane. The cell membrane is composed of a lipid bilayer, which contains proteins that function as ion channels and receptors. Compounds that disrupt the membrane environment can directly or indirectly alter the normal function of these proteins. In each cell, there are numerous subcellular organelles, all of which are potential targets for toxicity. Cytochrome P450 enzymes in the endoplasmic reticulum may metabolize drugs that enter the cell. Metabolism has one of two effects on the drug s potential toxicity (l)it may reduce toxicity by eliminatingparent compound, or (2) it may increase toxicity by generating a reactive (electrophilic) metabolite. Drugs may inhibit critical functions in mitochondria or damage DNA in the nucleus, which can lead to cell death by apoptosis or necrosis.

The trend in liver retention (not Illustrated) does not show the pronounced uptake for trans-[Pt(NH3)2Cl2] as in the kidney. Thus, the chemlcal-blogical processes leading to tissue retention (and perhaps organ toxicity) appear quite different for the liver V8 kidney. In this context, it is worthwhile to note that while uptake of cis-[Pt(NH3)2CI2] in the kidney can lead to nephrotoxicity, reports of hepatotoxicity associated with cis-[Pt(NH3)2CI2] chemotherapy are rare. 

In animal studies, decreased zinc status also contributes to lead and cadmium toxicity. In studies with rats, Cerklewski and Forbes (1976) demonstrated that an increase of zinc in the diet decreased the tissue lead levels and reduced other indicators of lead toxicity. Cerklewski (1979) also demonstrated that high levels of zinc fed to pregnant rats resulted in significantly lower levels of lead in the blood and liver of the rat pups. Using Japanese quail, Jacobs et al. (1977) reported that supplemental zinc markedly decreased concentrations of cadmium in the liver, kidney and small intestine, while Fox et al. (1979) showed that marginally adequate levels of dietary zinc markedly increased retention of cadmium in the duodenum, jejunum, ileum and liver as compared with zinc-supplemented birds. The association between increased lead burdens and lower serum zinc levels in children was reported by Markowitz and Rosen (1981). However, the mean levels of serum zinc in the children with elevated blood lead levels were not considered to be outside the lower limits of normal for plasma cited by Hambidge (1977). 

Lead toxicokinetics serves two critical roles in the delineation of lead toxicity. First, it provides the kinetic imderpinnings for expressions of lead intoxication in humans and other species. The rate of Pb entry into, and deposition within, tissues and cellular organelles is a prerequisite for toxic expressions with differing Pb exposiures. 

SubceUular distribution of Pb in human soft tissues appears to mainly involve the mitochondria and nuclei, two organelles known to either be affected toxicologically by lead or be involved in Pb sequestration and toxicokinetics. Intranuclear inclusion bodies, for example, have long been known to form as a transitory protective mechanism for averting or delaying lead toxicity. Lead in relatively large amounts is sequestered in nuclear inclusions and the biochemical and structural characteristics of these bodies have been described (Carroll et al., 1970 Moore et al., 1973). Cramer et al. (1974) showed the formation of intranuclear inclusions as an early response to Pb in kidney proximal tubule cells in new lead workers. 

Patterson has suggested that the levels of lead now present in the blood and tissues of modem man are very much higher than those prevailing in preindustrial times and that the natural level in blood corresponding to the conditions under which man evolved, is around 0.0025 ppm. On the basis of this view, what are now usually regarded as normal lead levels in Western Society could be indicative of lead toxicity at a sub-clinical level. If this is the case, we can expect children to be particularly affected, since they are known to be susceptible and there is a well-known association between lead toxicity and... 

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