Rn Toxicology: Chapter 23

antacids and buffered analegsics

peptic ulcer

mania and bipolar disorders

artritis

zinc

potassium

iron

phosphate

sulfate

metal binding proteins; essential to metal homeostasis and detoxicification; small, soluble, rich in thiol ligands; highly inducible by a variety of metals

glcoprotein that binds most of the ferric iron in plasma and helps transport iron across cell membranes

primarily a storage protein for iron; may serve as a general metal-detoxicant protein by binding a variety of toxic metals

copper-containing glycoprotein in plasma

may be carcinogenic; displace redox active essential elements; replaces but does not behave

fetal: toxicity of metals is well documented and many are teratongenic; younger subjects: often more sensitive to metal intoxication (neurotoxicity); elderly: more susceptible to metal toxicity than younger adults

metals can be reactive and site of entry is orften initially the organ most affected; children absorb more through gastrointestinal tracts

smoking or alcohol ingestion may have direct or indirect impacts on metal toxification; composition of diet can alter gastrointestinal absorption of various metals

concentration in blood or urine; expression of genes that play protective roles against metal toxicity

metal chelators: binds to metals; sulfhydrl groups

metalloid; inorganic trivalent compounds: arsenic trioixde and sodium arsenite; inorganic pentavalent compounds: sodium arsenate , arsenic acid, and pentoxide

trivalent methylated arsenicals are highly toxic

thiol reactive and can inhibit enzymes or alter proteins

uncouplers of mitochondrial oxidative phosphorylation by substitution of arsenate for inorganic phosphate in the formation of ATP

oral chelators penicillamine and succimer (DMSA or DMPS)

primarily exists in the divalent form (Pb2+); not biodegradable; absorption can be enhanced by low dietary iron and calcium

may act as a surrogate for calcium and disrupt calcium homeostasis

chelation therapy; oral chelating agent DMSA and succimer

liquid at room temp; vapor is much more hazardous; binds to other elements to form inorganic mercurous or mercuric salts; can form organometallic compounds when bond to carbon; methylmercury is most common

high-affinity binding of divalent mercury to sulfhydrl groups of proteins is important mechanism for producing nonspecific cell injury and death

direct to lower concentration at target organ; chelating agents such as cysteine, EDTA, BAL, or penicillamine

ranked one of the most toxic substances; gastronintestinal absorption increases when deficiencies of calcium or iron; transported in the blood by binding to proteins; also deposited in the liver and kindey to synthesize methallothionein (MT)

no clinical treatment; some chelators can reduce acute mortality but generally results in adverse effects

combines with carbon monoxide to form nickel carbonyl; nickel carbonyl is very toxic

blood nickel levels are indicated from chelation therapy; sodium diethylcarbodithioate (DDTC) is perferred; disulfiram, D-penicillamine and DMPS also work

D-penicillamine, Trien (triethylene tetramine 2HCl), zinc acetate, and tetrathiomolybdate; tetrathiomolybdate amd since acetate are more effective

essential metal for erythropoiesis and key component of hemoglobin, myoglobin, and other enzymes

supportive thereapy and iron chelation with defroxamine