A combination of resveratrol and 3,3′-diindolylmethane, a potent radioprotector

Abstract

Purpose: Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3′-Diindolyl methane (DIM) for its efficacy for radioprotection. It is our hypothesis that this combination that possesses less toxicity than synthetic compounds, free radical scavenging potential, and the capacity to interfere with the several of the signaling cascades that trigger damage to cell by ionizing radiation may possess good radioprotective capability.

Materials and methods: Mice were pre-treated with a combination of RSV and DIM and the 30-day mortality assay, endogenous antioxidant levels in intestinal mucosa, metaphase chromosomal aberrations, and micronuclei formation were assessed after exposed to ionizing radiation.

Results: The dose modifying factor (DRF) obtained for RSV, DIM, and the combination is 1.15, 1.17, and 1.3, respectively. Pre-treatment of mice with the combination results in significant (***p = .001) protection of the endogenous antioxidant levels, chromosomal aberrations, micronuclei formation, after exposure to ionizing radiation.

Conclusions: Our findings suggest that pre-treatment with the combination of RSV and DIM protects effectively from the ionizing radiation-induced damage at the molecular, cellular, and tissue levels by counteracting both the direct and indirect effects.

Keywords:

• Ionizing radiation
• resveratrol
• 3,3′-diindolylmethane
• micronuclei
• chromosomal aberrations
• radioprotection

Acknowledgments

The authours are grateful to Dr. Ramadasan Kuttan, Amala Cancer Research Center for providing lab facilities for in vivo studies and suggestions. Our thanks to Dr. R. P. Tripathi and Dr. B. Dwarakanate for helpful discussions.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

We would like to acknowledge Defence Research and Development Organization (DRDO), Ministry of Defence, Govt. of India, for providing financial support [grant number: DLC/81/48222/LSRB-269/SH&DD/2013].

Notes on contributors

Dithu Thekkekkara

Ms. Dithu Thekkekkara is interested in pharmacological aspects of natural products.

Duraiswamy Basavan

Prof. B. Duraiswamy has been leading extensive research on medicinal plants and natural products.

Sudhir Chandna

Dr. Sudhir Chandna works on insect cell radio-resistance, low-dose hyper-radio sensitivity and the unusual radiation responses of natural systems.

Moola Joghee Nanjan

Prof. M. J. Nanjan’s interests include drug design/development, natural products and radio-protection.