High-altitude medicines: a short-term genotoxicity study

Area of Science:

• Pharmacology
• Genetics
• Altitude Medicine

Background:

• High-altitude sickness affects populations globally due to reduced oxygen and barometric pressure.
• Marketed medicines are used for managing high-altitude ailments, but their genotoxic profiles are often unexamined.
• Genotoxicity assessment is crucial for drug safety, especially for conditions requiring prolonged treatment.

Purpose of the Study:

• To evaluate the genotoxic potential of six commonly marketed drugs used in high-altitude sickness management.
• To assess DNA damage in human blood cells exposed to these medications.
• To provide data for informed clinical decisions regarding drug use at high altitudes.

Main Methods:

• Utilized the comet assay (single-cell gel electrophoresis) to assess genotoxicity.
• Tested six medications on human peripheral whole blood cells and isolated lymphocytes.
• Evaluated DNA damage using percentage Tail DNA (% Tail DNA) and olive tail moment (OTM) at varying concentrations (250 microg/mL, 500 microg/mL, 1 mg/mL).

Main Results:

• Dexamethasone, deriphylline, and furosemide induced significant DNA damage in both whole blood and lymphocytes.
• Acetazolamide, ibuprofen, and nifedipine exhibited no genotoxic effects on human blood cells.
• % Tail DNA and OTM were sensitive and reliable indicators of genotoxicity across tested samples.

Conclusions:

• Dexamethasone, deriphylline, and furosemide warrant cautious use due to observed genotoxicity.
• Acetazolamide, ibuprofen, and nifedipine appear safer from a genotoxic perspective for high-altitude sickness management.
• Further in vitro mutagenicity and in vivo genotoxicity studies are recommended for a comprehensive safety profile.