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Sensitive "release-on-demand" fluorescent genosensors for probing DNA damage induced by commonly used cardiovascular
Sara S Mourad1, Magda A Barary1, Amira F El-Yazbi1
1Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Alexandria University, 1 El Khartoum Square, Alexandria 21521, Egypt.
Insights
Cardiovascular drugs (CVDs) can cause DNA damage when exposed to UVA radiation, as shown by bioluminescent genosensors. This interaction highlights potential risks associated with drug-radiation exposure.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Cardiovascular disorders are a leading cause of global mortality.
- Chronic use of cardiovascular drugs (CVDs) can lead to drug-radiation interactions.
- Drug-radiation interactions may cause photosensitization, leading to DNA damage, mutagenesis, and cancer.
Purpose of the Study:
- To investigate potential DNA damage induced by frequently used CVDs following UVA irradiation.
- To assess the interaction between specific CVDs and DNA using bioluminescent genosensors.
- To evaluate the utility of terbium chloride and EvaGreen genosensors for detecting DNA-drug interactions.
Main Methods:
- Application of two bioluminescent genosensors: Terbium chloride and EvaGreen.
- Investigation of ten commonly prescribed CVDs: Amiloride, Atorvastatin, Captopril, Enalapril, Felodipine, Hydrochlorothiazide, Indapamide, Losartan, Triamterene, and Valsartan.
- Confirmation of DNA damage and drug-DNA interaction using viscosity measurements and calf thymus DNA.
Main Results:
- All ten studied CVDs induced DNA damage upon UVA irradiation.
- The induced DNA damage proportionally altered the fluorescence of both terbium chloride and EvaGreen genosensors.
- Viscosity measurements indicated possible intercalation of CVDs with DNA, confirming the observed damage.
Conclusions:
- Frequently used cardiovascular drugs can induce DNA damage following UVA irradiation.
- Bioluminescent genosensors offer a simple, automated, and cost-effective method for assessing DNA-drug interactions.
- The findings highlight potential risks of drug-radiation interactions and the importance of genotoxicity assessment for CVDs.
Abstract:
Cardiovascular drugs (CVDs) are agents working on the heart and the vascular system to treat many cardiovascular disorders. Such disorders represent the leading cause for morbidity and mortality worldwide. The treatment regimen includes different administered drugs on chronic basis. The cumulative drugs in human body coincides with exposure to electromagnetic radiations from different sources leading to drug-radiation interaction that may lead to drug photosensitization. Such photosensitization may lead to mutagenesis, cancer, and cell death due to molecular damage to DNA. This work involves the application of two bioluminescent genosensors; Terbium chloride and EvaGreen are utilized to investigate potential DNA damage caused by frequently used CVDs following UVA irradiation. A variety of CVDs are investigated. Ten drugs; Amiloride, Atorvastatin, Captopril, Enalapril, Felodipine, Hydrochlorothiazide, Indapamide, Losartan, Triamterene and Valsartan are studied. The study's findings showed that such drugs induced DNA damage following UVA irradiation. The induced DNA damage altered the fluorescence of terbium chloride and EvaGreen genosensors, proportionally. The results are confirmed by viscosity measurements reflecting the possible intercalation of CVDs with DNA. Also, the work is applied on calf thymus DNA to mimic the actual biological variability. The demonstrated bioluminescent genosensors provide automatic, simple and low-cost methods for assessing DNA-drug interactions.
