Ethyl Pyruvate as Potential Countermeasure against Gamma Irradiation-Induced DNA Damage

Posted: 6 Feb 2020

See all articles by Deepti Sharma

Deepti Sharma

Institute of Nuclear Medicine and Allied Sciences

Lajpreet Kaur

Institute of Nuclear Medicine and Allied Sciences

Mallika Pathak

University of Delhi - Miranda House

Vinod Kumar

Institute of Nuclear Medicine and Allied Sciences

Himanshu Ojha

Institute of Nuclear Medicine and Allied Sciences

Date Written: February 4, 2020

Abstract

60Co Gamma irradiation causes 70% of indirect DNA damage via forming free radicals out of water radiolysis. Most of these reactive oxygen species (ROS) are neutralized through the natural mechanism i.e., intrinsic antioxidants. However, excess oxidant production results in oxidative stress, then there occurs a need to monitor the oxidative stress using exogenous agents or antioxidants. Ethyl pyruvate (EP), a synthetic derivative of pyruvate, which is a substrate in Kreb’s cycle. EP possesses an immense ROS scavenging property. The present study has investigated ROS scavenging and DNA binding property of EP, protecting DNA from the sub-lethal dose (45 Gy) of gamma radiation. Antioxidant assays, DPPH and FRAP shows the increasing in the dose of EP, it scavenges the ROS effectively. The binding studies such as UV-Vis spectroscopy and circular dichroism showed that EP binds weakly with the DNA but provides significant protection. The molecular docking analysis of EP and DNA revealed that the EP binds in the minor groove of DNA with the docking score of -3.75 kcal/mol and as an intercalator with a docking score of -4.25 kcal/mol. Ethidium bromide (EtBr) exclusion assay indicates that a small amount of EP binds to the DNA through intercalative mode. The plasmid relaxation study signifies that in the presence of a sub-lethal dose of gamma radiation, EP protects DNA.

Suggested Citation

Sharma, Deepti and Kaur, Lajpreet and Pathak, Mallika and Kumar, Vinod and Ojha, Himanshu, Ethyl Pyruvate as Potential Countermeasure against Gamma Irradiation-Induced DNA Damage (February 4, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020. Available at SSRN: https://ssrn.com/abstract=3531470

Deepti Sharma (Contact Author)

Institute of Nuclear Medicine and Allied Sciences ( email )

Delhi
India

Lajpreet Kaur

Institute of Nuclear Medicine and Allied Sciences ( email )

Delhi
India

Mallika Pathak

University of Delhi - Miranda House ( email )

University Road
Kirti Nagar
Delhi, DE New Delhi 110 007
India

Vinod Kumar

Institute of Nuclear Medicine and Allied Sciences ( email )

Delhi
India

Himanshu Ojha

Institute of Nuclear Medicine and Allied Sciences ( email )

Delhi
India

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