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Contrast medium- and mannitol-induced apoptosis in heart and kidney of SHR rats
1Division of Applied Pharmacology Research, Center for Drug Evaluation and Research (HFD-910), Food and Drug Administration, Laurel, Maryland 20708, USA.
Insights
Contrast media and mannitol induce apoptosis in rat hearts and kidneys. Higher osmolality correlated with increased apoptosis, suggesting different mechanisms for contrast media and mannitol in causing cell damage.
Area of Science:
- Nephrology
- Cardiology
- Toxicology
Background:
- Contrast media (CM) and mannitol (M) are commonly used in medical procedures.
- Potential cardiorenal toxicity of CM and M requires investigation.
Purpose of the Study:
- To investigate the induction of apoptosis by CM and M in the hearts and kidneys of Sprague Dawley rats.
- To explore the mechanisms by which CM and M induce apoptosis.
Main Methods:
- Ten groups of rats received different concentrations of CM (Hypaque, Omnipaque) or M, or saline.
- DNA fragmentation was detected using TUNEL assay.
- Immunohistochemistry was used to assess Bcl-2, Bax, and p53 expression in kidneys.
Main Results:
- Apoptosis was observed in cardiac and renal cells, including myocytes, tubular, glomerular, vascular endothelial, and smooth muscle cells.
- Increased apoptosis frequency correlated significantly with increased osmolality of CM and M.
- CM treatment led to increased Bax and p53, and decreased Bcl-2, while M treatment did not alter these markers.
Conclusions:
- CM and M activate cardiac and renal apoptosis through distinct mechanisms.
- Apoptosis induced by CM and M may contribute to acute heart and kidney damage.
Abstract:
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.