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Contrast Medium- and Mannitol-Induced Apoptosis in Heart and Kidney of SHR Rats

Division of Applied Pharmacology Research, Center for Drug Evaluation and Research (HFD-910), Food and Drug Administration, Laurel, Maryland 20708, and

Cristobal G. Duarte

Division of Cardio-Renal Drug Products, Center for Drug Evaluation and Research (HFD-110), Food and Drug Administration, Rockville, Maryland 20857

Sydney Ellis

Division of Applied Pharmacology Research, Center for Drug Evaluation and Research (HFD-910), Food and Drug Administration, Laurel, Maryland 20708, and

The induction of apoptosis by contrast media (CM) and mannitol (M) was investigated in the hearts and kidneys of 12-mo-old male SHR rats. Ten groups of 3 SHR rats received a dose of 5 ml/kg of one of the following: Hypaque (H)-30. H-60, H-76, Omnipaque (O)-140, O-350, mannitol (M)-4%, M-9%, M-19%, M-27%, or saline (S). DNA fragmentation was detected using the terminal deoxynucleotidyl transferase-mediated [TdT] dUTP nick-end labeling (TUNEL) method, and the morphology characteristics of apoptosis were confirmed in cardiac and renal cells. The immunoreactivities of Bcl-2, Bax, and p53 were assessed immunohistochemically in the kidneys. Apoptosis occurred in cardiac myocytes and renal tubular and glomerular cells as well as in vascular endothelial and smooth muscle cells of the heart and kidneys. The high frequency of apoptosis correlated significantly with the increase in the osmolality of the H, O, and M. The increased Bax, the increased p53, and the decreased Bcl-2 immunoreactivities were detected in H- or O-treated, but not in M-treated, rats. These findings suggest that CM and M activate cardiac and renal apoptosis by different mechanisms and that the apoptotic process may be implicated in acute heart and renal damage.

Key Words: Cardiotoxicity • nephrotoxicity • terminal deoxynucleotidyl transferase-mediated [TdT] dUTP nick-end labeling (TUNEL) • Bcl-2 • Bax • p53 • osmolality

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Toxicologic Pathology, Vol. 27, No. 4, 427-435 (1999)
DOI: 10.1177/019262339902700406


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This Article Abstract Free Full Text (Free PDF) Free 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 Google Scholar Citing Articles via Scopus Google Scholar Articles by Jun Zhang Articles by Ellis, S. Search for Related Content PubMed PubMed Citation Articles by Jun Zhang, Articles by Ellis, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB D-MANNITOL Social Bookmarking                         What's this?