ABSTRACT
To investigate the relationship between cadmium (Cd) toxicity, intestinal absorption, and its distribution to various tissues in rats treated orally with minimum amounts of Cd, 14 female rats per dose group per time point were given diets consisting of 28% purified diet and 72% ordinary rice containing Cd-polluted rice (0. 02, 0.04, 0.12, or 1.01 ppm of Cd) or CdCl(2) (5.08, 19.8, or 40.0 ppm of Cd) for up to 8 months. At 1, 4, and 8 months after the commencement of Cd treatment, seven rats per group were euthanized for pathological examinations to determine the Cd concentrations in the liver and kidneys and metallothionein (MT) in the liver, kidneys, intestinal mucosa, serum, and urine. One week before each period of 1, 4, and 8 months, the remaining seven rats in each group were administered a single dosage of (109)Cd, a tracer, to match the amounts of the designated Cd doses (about 1.2 to 2400 microg/kg body wt). They were euthanized 5 days later to determine the distribution of Cd to various tissues. No Cd-related toxic changes were observed. The concentrations of Cd in the liver and kidneys at any time point and MT in the liver, kidney, serum, and urine at 4 and 8 months increased dose-dependently, whereas MT in the intestinal mucosa did not alter markedly at any time point. The distribution rates of Cd to the liver increased dose-dependently (40% at lower doses to 60% at higher doses), whereas those to the kidney decreased dose-dependently (20% at lower doses to 10% at higher doses). The Cd retention rates 5 days after (109)Cd administration (amounts of Cd in various tissues/amounts of Cd administered) ranged from 0.2 to 1. 0% at any time point. These results suggest that the distribution of Cd to the liver and kidneys after the oral administration vary depending on the dosage levels of Cd. The difference of the distribution pattern of Cd to the liver and kidney is probably due to the difference in the form of the absorbed Cd, i.e., free ion or Cd-MT complex, although not closely related to the MT in the intestinal mucosa.
Subject(s)
Cadmium/pharmacokinetics , Food Contamination , Administration, Oral , Animals , Body Weight , Cadmium/administration & dosage , Cadmium/toxicity , Cadmium Chloride/pharmacokinetics , Cadmium Radioisotopes , Diet , Female , Metallothionein/blood , Metallothionein/metabolism , Metallothionein/urine , Oryza , Rats , Rats, Sprague-Dawley , Time Factors , Tissue DistributionABSTRACT
The usefulness of immunohistochemistry is usually confined to qualitative analysis. Quantitative evaluation is not performed. At best, the number of immunopositive cells and the immunointensities are recorded as several grades, to which a strict categorization may be applied by individual examiners, but these categorizations are not standardized. We have attempted to quantify immunohistochemical observations using an image analyser. Sections from rat pituitary adenomas secreting prolactin and growth hormone were immunostained for these hormones with either immunogold silver or avidin-biotinylated peroxidase complex (ABC) methods. The number of immunopositive cells were counted by eye on specimens stained with the ABC method. In sections stained by an immunogold-silver technique, an immunopositive area was measured at several immunointensity ranges, to which certain points were allotted. Immunohistochemical values obtained by summing the products of the immunopositive area and intensity points at each range were correlated with concentrations of hormones in adenoma tissues measured by radioimmunoassay. A high correlation between the immunohistochemical values and hormone concentrations were shown for both prolactin and growth hormone, in contrast to a low correlation between the number of immunopositive cells counted by eye and the hormone concentrations. These findings indicate that the immunohistochemical observations can be quantified using the image analyser to the extent that they can be substituted, albeit roughly, for the hormone concentrations measured biochemically.