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Absence of DNA damage in mice and rats given high doses of five beta-adrenergic blocking agents
Abstract:
Five beta-blockers (propranolol, metoprolol, oxprenolol, pindolol, and sotalol) were tested for their in vivo DNA-damaging activity by two different techniques: alkaline denaturation of DNA followed by hydroxylapatite chromatography, and a new viscometric method markedly more sensitive in detecting DNA fragmentation. DNA damage, as checked by the first technique, was absent either in liver and kidney of mice or in liver and gastric mucosa of rats given a single p.o. administration of 1/2 LD50 of the drugs. The subsequent viscometric analysis of liver DNA from rats treated with the same doses confirmed the above negative results.
Insights
This study found no evidence of DNA damage in animal models treated with five common beta-blockers. Tests on mice and rats confirmed the safety of propranolol, metoprolol, oxprenolol, pindolol, and sotalol regarding genotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Molecular Biology
Background:
- Beta-blockers are widely prescribed cardiovascular drugs.
- Assessing the in vivo genotoxic potential of pharmaceuticals is crucial for patient safety.
Purpose of the Study:
- To evaluate the in vivo DNA-damaging activity of five beta-blockers: propranolol, metoprolol, oxprenolol, pindolol, and sotalol.
- To compare the sensitivity of two distinct methods for detecting DNA fragmentation.
Main Methods:
- In vivo administration of 1/2 LD50 of beta-blockers to mice and rats.
- Analysis of DNA damage using alkaline denaturation followed by hydroxylapatite chromatography.
- Assessment of DNA fragmentation using a sensitive viscometric method.
Main Results:
- No DNA damage was detected in the liver and kidney of mice.
- No DNA damage was observed in the liver and gastric mucosa of rats.
- Viscometric analysis of rat liver DNA corroborated the absence of DNA fragmentation.
Conclusions:
- The tested beta-blockers (propranolol, metoprolol, oxprenolol, pindolol, sotalol) do not exhibit in vivo DNA-damaging activity at the tested doses.
- Both alkaline denaturation and viscometric methods confirmed the lack of genotoxicity.
- These findings support the safety profile of these beta-blockers concerning DNA integrity.