Robert A. Goyer

Lead dosage and the role of the intranuclear inclusion body. An experimental study.

Biological parameters known to be affected in lead poisoning were measured in rats following ingestion of graded dosages of lead. Intranuclear inclusion bodies are formed in renal tubular lining cells with smaller doses of lead than produce other changes. Decreased body weight is the next most sensitive abnormality. This is followed by increased delta-aminolevulinic acid (ALA) excretion, reticulocytosis, renal edema, and aminoaciduria. Anemia only occurs at the highest lead dosage. Over a wide range of lead ingestion, urinary lead excretion remains constant, although renal lead content increases. Quantitative lead analyses of cell organelles show that lead is concentrated within the inclusion bodies. Relatively small amounts of lead are present in the cytoplasm and mitochondria. It is suggested that soft-tissue lead accumulates in the intranuclear inclusion body, thereby sparing toxic injury to cytoplasmic organelles.

Intracellular effects of chronic arsenic administration on renal proximal tubule cells

Arsenic is one of the more common toxic elements in the environment. The kidney accumulates this element and plays a major role in its metabolism and excretion. Mitochondria have been found in vitro to be highly sensitive to the toxicity of this element. Combined oxygen electrode and electron microscopic studies were conducted on kidneys of rats exposed to arsenate in the drinking water at concentrations of 40, 85, or 125 ppm for 6 weeks to evaluate in vivo mitochondrial toxicity. Decreased state 3 respiration and respiratory control ratios were observed in kidneys of rats given the 85 and 125 ppm dose levels. Ultrastructural alterations, which consisted of swollen mitochondria and increased numbers of dense autophagic lysosome-like bodies, were confined to proximal tubule cells of these same animals. This study places renal arsenate mitochondrial toxicity into an in vivo context and points to the value of using complementary techniques for assessing the subacute or chronic toxicity of environmental agents.

Cytochrome content of kidney mitochondria in experimental lead poisoning

Abstract Cytochromes aa 3 , b , c 1 , and c were quantitated in isolated renal mitochondria of control and lead poisoned rats. Lead poisoning was induced by ingesting a diet containing 1% lead as lead acetate. Concentration of cytochrome aa 3 was decreased in the lead-poisoned animals when related to mitochondrial protein. On the basis of kidney DNA, cytochrome aa 3 , and b were also significantly reduced. The protein content of mitochondria from the experimental animal was decreased 18%. Kidney homogenate protein was decreased by about 11%. The lead effect is attributed to inhibition of either porphyrin synthesis or protein synthesis. It is suggested that the observed reduction in cytochrome content may be at least in part responsible for the respiratory abnormality that occurs in renal mitochondria of lead-poisoned rats.