The nature of low-molecular-weight proteinuria, which were observed in rabbits given nephrotoxic compounds such as cadmium, kanamycin, uranium, mercury or chromium, were studied in the present experiment : rabbits were given subcutaneous injections of cadmium 6 times a week at a dose level of 0.5 mgCd/kg over a period of 32 weeks. Main components of proteins in urine of cadmium-treated animals were proteins of molecular weight 67, 000 (probably albumin) and higher-molecular-weight, and that might suggest the existence of tubular dysfunc-tions as well as of glomerular dysfunctions. Rabbits given a single injection of uranium, chromium or mercury indicated low-molecular-weight proteinuria as well. Molecular weight distribution of proteins in urine of the uranium-, chromium-or mercury-treated rabbits were hardly distinguishable from that of cadmium-treated rabbits. Low-molecular-weight proteinuria appeared in spite that tubular reabsorp-tion of phosphorus was higher than 80%. The mechanism of low-molecular-weight proteinuria was discussed.
Sodium dodecyl sulfate (SDS) acrylamide gel electrophoretic studies were performed on low-molecular-weight (LMW) proteins in urine from rabbits given sub-cuteneous injections of cadmium chloride at a dose level of 0.5mgCd/kg over a period of 42 weeks to evaluate the procedure for screening early effects of cadmium : in the 1st week, a gradual increase in urine cadmium was found ; in the 3rd week, slight LMW proteinuria (proteins of MW 12, 000 and 25, 000); in the 6th week, slight protein-uria, (proteins mostly of MW 67, 000); in the llth-13th week, aminoaciduria, glycos-uria, proteinuria and LMW proteinuria (proteins of MW 12, 000 and 25, 000). As shown above, protein of MW 12, 000 (probably β2-microglobulin) and 25, 000 (pro-bably retinol-binding protein) increased in urine a little earlier than protein of MW 67, 000 (probably albumin) in rabbits given cadmium. Therefore, urine LMW pro-teins were thought to be effective indices for screening early effects of cadmium. Sixty-80% of proteins in urine from rabbits given cadmium were proteins of MW 67, 000, while only 10% were LMW proteins. This fact might suggest that cadmium affect tubules as well as glomerules.
A periodic study of biochemical and histopathological changes in the stomach of guinea pigs, was carried out at 6, 12 and 24 hrs after oral admini-stration of 500 mg of chrysotile dust. The gastric juice showed a significant increase in volume, free and total acidity and peptic activity. A marked reduction in mucin contents, most significantly at 12 hrs also occurred. Significant dissolution of nickel and a parallel rise in ATPase activity of gastric mucosa was also observed. Histopathologically mucosa' injury was evident at 12 hrs but regressed by 24 hrs. The changes in acidity of gastric juice and dissolution of nickel are discussed with reference to their role in gastric ulceration or carcinoma by ingested asbestos.
A simplified and accurate assay method for measuring 3-methoxy-4-hydroxy mandelic acid (VMA) in human urine was established. The method is thought to be applicable to the assay of a large number of samples at one time. VMA concentration in human urine was determined spectrophotometrically after purification of the VMA and its conversion to vanilline. The extraction of VMA and vaniline from the medium into the organic solvent and their purification depend largely on pH, of which the indicator is an excellent reagent for the conversion of VMA to vanilline. The normal value of VMA in the urine of eight healthy young resting males (20-24 years old) was found with this method to be 41.4± 21.3 moles/ min (the mean±S.D.).
To investigate intracellular metal transport systems in the liver in vivo, male mice were given a single, intraperitoneal dose of Mn(CH3C00)2•4H2O (49 mg/kg), CuSO4•5H20 (6 mg/kg), K2Cr2O7 (15 mg/kg), or Pb(CH3COO)2•3H2O (38 mg/kg). High concentrations of Mn in the liver were rapidly recovered in both lysosomal and mitochondrial fractions and seemed to excrete into bile via liver lysosomes. The normal distribution of Ca in the subcellular fractions and bile was quite similar to that of excessive Mn. Following injection of Mn, Ca content in the liver mito-chondria increased but decreased in bile. Absorbed Cu, Pb, Cr and normal Zn in the liver were mainly recovered in the soluble fraction. Most absorbed Cu, Pb and normal Zn in the soluble fraction was bound to high-molecular-weight sub-stances, however, most excessive Cr was bound to a low-molecular-weight substance. Cr content decreased more rapidly than Cu and Pb content in the soluble fraction. Metal concentrations recovered in the liver lysosomes and excreted in bile were in the following order : Ca, Mn>Zn, Cu>Cr, Pb. These results suggest that biliary excretion of these metals, especially Mn and Ca, is primarily dependent on lysosomal metal uptake and release, and that the nature of metal binding substances for Cu, Pb, Cr and. Zn affects their transport systems in liver.
Pregnant and nonpregnant rats were administered 500 ppm of lead in drinking water for 23 days. Pregnant and nonpregnant rats administered dis-tilled water served as controls. Red blood cell counts, hematocrit and hemoglobin were significantly decreased in the pregnant rats, but there were no significant dif-ferences between the control and the lead-treated group. Erythrocyte delta amino-levulinic acid (ALAD) activity was significantly reduced in the lead-treated group. In the lead-treated group, there was tendency for stronger depression of erythrocyte AL AD activity in pregnant rats. Furthermore, AL AD activity of the liver and spleen were significantly decreased in the lead-treated pregnant rats. In the lead-treated group, the lead (Pb) concentrations of blood, liver and spleen were higher in pre-gnant than in nonpregnant rats. The erythrocyte ALAD activity is negatively cor-related with the blood Pb concentration in pregnant and nonpregnant rats. A statistically significant correlation between the ALAD activity and the Pb concen-tration of the tissues were observed only in pregnant rats. These results indicate that special avoidance of lead exposure should be required for mothers during pregnancy.
Polygraphic recordings of circadian sleep-waking rhythms of rats were made before and after oral administration of methylmercury chloride (MMC). MMC-dosed rats exhibited an increase in both dark-phase slow wave sleep (SWS) and paradoxical sleep (PS) and a decrease in light-phase PS. There was no difference in the amounts of both light-phase SWS and wakefulness (W) before and after MMC administration. A phase of the circadian PS rhythm was dissociated after MMC administration, whereas the circadian SWS rhythm was still entrained synchron-ously to a light/dark cycle. The MMC-induced sleep disorder returned to the original sleep patterns by Days 35-55 after MMC administration. Possible mechan-isms underlying the sleep disorder are discussed in light of the reported cholinergic dysfunctions of the central nervous system. The appearance of sleep disorder is compared with that of neurological signs of motor incoordination and changes in brain Hg concentrations with time. The onset of neurological signs of staggering gait of MMC-dosed rats coincided with the time when brain Hg concentrations reached maximum levels.