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Side effects of rapamycin in the rat
1Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Summary
Rapamycin treatment in rats showed dose-dependent cardiac side effects, including myocardial infarction at higher doses (1.0 and 1.5 mg/kg/day). Lower doses (0.5 mg/kg/day) did not cause cardiac toxicity, and kidneys remained unaffected.
Area of Science:
- Pharmacology
- Toxicology
- Histopathology
Background:
- Rapamycin is an immunosuppressant drug with potential toxicities.
- Understanding Rapamycin's side effects is crucial for its clinical application.
Purpose of the Study:
- To evaluate the histopathological side effects of Rapamycin in the heart, kidneys, and eyes of Lewis rats.
- To determine the dose-dependent toxicity of Rapamycin.
Main Methods:
- Lewis rats were administered Rapamycin intravenously for 14 days.
- Doses administered were 0.5, 1.0, and 1.5 mg/kg/day.
- Histopathological examination of cardiac, renal, and ocular tissues was performed.
Main Results:
- Focal myocardial infarction occurred in rats receiving 1.5 mg/kg/day (3/5) and 1.0 mg/kg/day (2/22).
- No myocardial toxicity was observed at 0.5 mg/kg/day.
- One rat at 1.5 mg/kg/day showed focal ischemic necrosis in the retina; kidneys were normal across all doses.
Conclusions:
- Rapamycin exhibits dose-dependent cardiotoxicity, with myocardial infarction observed at higher doses.
- Ocular toxicity was minimal, and renal toxicity was not observed within the tested dose range.
- Careful dose monitoring is recommended to mitigate Rapamycin-induced side effects.