This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Tanimoto, A. Articles by Koide, O. Search for Related Content PubMed PubMed Citation Articles by Tanimoto, A. Articles by Koide, O. Social Bookmarking                         What's this?

Cell Death and Regeneration of Renal Proximal Tubular Cells in Rats with Subchronic Cadmium Intoxication

Department of Pathology and Toxicologic Pathology

Tetsuo Hamada

Department of Surgical Pathology, University of Occupational and Environmental Health, Japan 1–1, Iseigaoka, Yahatanishi-ku, Kitakyashu 807, Japan

Osamu Koide

Department of Pathology and Toxicologic Pathology

Male Sprague-Dawley rats were injected subcutaneously with 0.6 mg cadmium (Cd)/kg/day for 8 wk. The subsequent changes in renal proximal tubules were studied histologically, histochemically, and ultrastructurally. The urinary and tissue Cd concentrations were determined by atomic absorption spectrophotometry. After 4 wk of exposure, apoptosis was observed predominantly in segment S3 along with epithelial regeneration in the affected tubules, and these changes gradually became more pronounced as the experimental period was prolonged. The apoptotic cells were shed into the lumen and were found to contain a large quantity of Cd. Apoptotic cells were counted in paraffin sections after various periods of exposure to Cd. Nuclear bromodeoxyuridine uptake, mitotic count, and nuclear density were used as indicators of tubular regeneration. A correlation was found between the numerical increase of apoptotic cells and the rate of urinary Cd excretion, and the rate of increase in the tissue Cd concentration had a tendency to reduce after 4 wk as the rate of urinary Cd increased. These observations suggest that apoptosis might be helpful for the efficient excretion of Cd into urine. Progressive increases in the preceding indicators of regeneration were observed. From our results, it appears that Cd-induced tubular damage, i.e., cell deletion due to apoptosis, is reversible as a result of marked epithelial regeneration. On the basis of these histological changes, the critical concentration of Cd required to produce renal tubular damage was estimated to be 600 µg/g dry tissue.

Key Words: Cadmium chloride • proximal tubule • apoptosis • regeneration • histopathology • ultrastructure • critical concentration

Toxicologic Pathology, Vol. 21, No. 4, 341-352 (1993)
DOI: 10.1177/019262339302100401


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				T. Yoshida, Y. Makita, T. Tsutsumi, S. Nagata, F. Tashiro, F. Yoshida, M. Sekuima, S.-I. Tamura, T. Harada, K. Maita, et al. Immunohistochemical Localization of Microcystin-LR in the Liver of Mice: A Study on the Pathogenesis of Microcystin-LR-Induced Hepatotoxicity Toxicol Pathol, May 1, 1998; 26(3): 411 - 418. [Abstract] [PDF]