Role of antioxidants in enhancing radioprotection: Insights from diagnostic radiology and radiotherapy studies

INTRODUCTION

In the past few decades, there has been a significant increase in the use of ionising radiation such as X-rays or gamma rays in both diagnostic and therapeutic radiology. The use of radiological investigation techniques, such as computed tomography or nuclear medicine imaging, has also been increasing significantly.^[1-5] Numerous advancements aim to reduce radiation exposure.

Even low doses of radiation can cause stochastic effects, such as cancer or mutant DNA, since there is no threshold for radiation damage.^[6] Numerous studies have found that exposure to radiation increases the risk of cancer, especially among youngsters.^[7,8]

Direct and indirect effects of radiation have equal potency to cause the radiation-induced damage.^[9] Free radicals [Figure 1], formed as a result of ionisation, will cause an indirect effect by breaking the covalent bond in the DNA and causing double-strand breakage. It causes either cell death or mutation.^[10,11]

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Figure 1:

Graphical representation of effects of ionising radiation on water molecule (indirect effect).

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Antioxidants are substances that counteract free radicals by providing an electron to neutralise them [Figure 2].^[12] Antioxidants such as glutathione, ubiquinol, melatonin and uric acids are produced in the body during metabolism. Some antioxidants, such as Vitamin C, Vitamin E, Selenium, Zinc and omega-3 fatty acids, must be obtained from dietary sources.^[13]

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Figure 2:

Representation of antioxidants neutralising free radical. Black dots: Electrons, White dot: hole (vacant), Arrow: donation of electron from antioxidant to free radical.

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Antioxidants could also neutralise free radicals produced due to the indirect effect of ionising radiation if it is administered before irradiation. The current article aimed to investigate antioxidants’ efficacy to protect against ionising radiation’s effects.

METHODOLOGY

RESULTS

Study selection

A total of 1003 articles were obtained using the phrases mentioned above. These articles were carefully analysed for inclusion criteria by reading their titles and abstracts. Further, the full-length articles were read by two reviewers to determine the total number of articles that qualify for the final review, which turned out to be 19 articles [Figure 3]. These selected articles contained data on antioxidants’ efficacy in reducing radiation’s effects in diagnostic and therapeutic radiology. Articles that were not available in English and those without full text were excluded from the study.

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Figure 3:

PRISMA chart for the articles included in this review. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

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ANTIOXIDANTS

Antioxidants are the molecules that readily donate electrons to free radicals to neutralise them, which otherwise would result in oxidative stress.^[13] The antioxidant administration before and/or after irradiation with ionising radiation such as X-ray or gamma rays to prevent DNA damage due to oxidative stress is investigated in this review. The antioxidants in which the studies included in this review are as follows: Melatonin, Vitamin C, Vitamin E, carotenoids, genistein, N-acetyl L-cysteine, selenium and metformin.

ANTIOXIDANTS AS RADIOPROTECTORS

DISCUSSION

The present study reviewed the efficacy of antioxidants in protecting tissues from radiation injuries. Since the use ionising radiation is the most important part of the health-care system in diagnosing disease to treat it, minimising the biological effects of radiation is very important.^[33] The study used various original articles which were performed to rule out the effectiveness of antioxidants in protecting DNA against radiation.

MDA was found to be increased in serum after irradiation with X or gamma radiation.^[32,34,35] This is the product of free radical generation due to oxidative stress in biological tissue after ionising radiation irradiation.^[36] LDH was found to increase after irradiation, which is another marker for any tissue damage like radiation injury or due to metastasis.^[37,38] Elevated serum troponine is the marker for cardiotoxicity, which was found post-radiotherapy.^[39] The review findings suggest that the administration of melatonin prior to irradiation will decrease MDA, LDH and troponine levels. Moreover, MDA level also decreased post-administration of resveratrol prior to irradiation. GGT, SGOT, SGPT and ALP are the markers which indicate the oxidative stress in liver cells.^[40-43] Elevation in all these three markers was found to be decreased in melatonin administered group post-irradiation, according to the review findings. Radiation decreases the SOD, CAT levels and GPx activity, which are responsible for reaction against reactive oxygen species.^[44,45] The review finding suggests that, the administration of melatonin or MitoEbselen-2 maintains these levels.

Irradiation with gamma rays causes various histological damages. In digestive system damages includes, mucositis signs, inflammation of cells, Brunner’s glands damage, goblet cells reduction, villi height and number reduction in jejunum and ileum.^[15,31]In testis, atrophy of seminiferous tubules, Leydig cell hyperplasia, basal lamina thickening, spermatogonia number reduction and Johnsen score reduction are most commonly seen.^[16,26] In renal system, proliferative lesions of glomeruli and wall thickness of Bowman’s capsule. Also thickness of muscle fibre or fibrosis in heart and hepatocyte ballooning, pyknotic nuclei formation and necrosis of liver are seen.^[19,22] The results from this review showed 100 mg/kg of melatonin administration before irradiation was able to reverse all these effects and antioxidant genistein 200 mg/kg was able to reduce liver necrosis. Furthermore, X-ray irradiation resulted in vitro growth inhibition of TIG 3 and MRC 5 cells in human lungs after a dose of 2.5 Gy.^[21] In vitro treatment of melatonin was able to increase the growth inhibition threshold to 5 Gy.

γH2AX assay is the most commonly used method to rule out the DNA double-strand breaks.^[46] This method is the most sensitive and reliable method to rule out radiation-induced DNA damage.^[47] The multiple studies included in the review suggested that the administration of antioxidants such as melatonin, Vitamin C, NAC, Q 10, ß-carotene, selenium and Vitamin E would result in decreased X-ray-induced γH2AX foci in human peripheral blood lymphocytes. Furthermore, a few other antioxidant’s mixtures also showed similar results as mentioned in the result. Furthermore, MN frequency and comet assay also are also mostly used techniques in biodosimetry. MN frequency and % comet tail formation increases with increase in ionising radiation dose.^[48,49] Melatonin administration was able to reduce both of these, including regulation of G-CSF and anti-apoptotic activity, according to the results of the review.

More number of studies on humans are needed for a stronger conclusion of the results. Since the majority of the studies are on rats, that was the major limitation of the study. Furthermore, comparison between antioxidants on a large scale is needed to find out which antioxidants can be used.

CONCLUSION

Administration of antioxidants prior to irradiation with X-rays or gamma rays would result in decreased biological damage. Multiple antioxidants were included in this review, out of which melatonin was the most used antioxidant. It was also effective in reducing all types of radiation damage.