In this study, we found in the irradiation alone group that LOOH,, TOS,, and OSI, which shows the level of oxidative damage, were higher than all the other groups. We found that in the lungs of rats given propolis together with cranial irradiation, all these markers were significantly lower than those of the irradiated group alone and were not different from the control groups, confirming our hypothesis.
Radiotherapy has both local and systemic toxic side effects. Systemic toxicity can be defined mainly as cytotoxic and genotoxic effects caused by oxidative damage caused by free radical formation due to ionizing radiation16. Recent studies have revealed a close relationship between the risk of heart disease and liver damage in individuals exposed to ionizing radiation (IR)17,18. Cardiac toxicity is dose-dependent and can present with different clinicopathological manifestations, such as inflammation, pericarditis, angina, myocardial necrosis, and late myocardial fibrosis. Hepatocyte degeneration, congestion, and dilatation in sinusoids increase in biochemical markers (ALT, AST, LDH) and deterioration in lipid profile are among the main changes.
Radiation given directly to the lungs or adjacent areas of the lung has local toxic effects. These are mainly pulmonary parenchymal inflammation, oxidative damage, DNA damage, apoptosis, radiation pneumonitis, which has an incidence of 5 to 20% and is characterized by type I pneumocyte damage, and radiation fibrosis with type I pneumocyte proliferation, which develops via cellular signal transduction secondary to cytokines such as interleukin 6 (IL-6)19. These clinicopathological processes contribute to the decrease in pulmonary reserve through ventilation, perfusion, or diffusion defects in both acute and chronic periods.
The systemic toxicity of oxygen radicals on lung tissue, which can be formed in different conditions other than radiation, has been proven. As a component of the systemic circulation, emerging damage in the lung is inevitable and is caused by cytokines and oxygen radicals secondary to oxidative damage. There is existing evidence that, regardless of the cause, increased oxidative stress and lipid peroxidation decreased in spirometric measurements of the functional capacity of the lungs and thus the level of FEV1 (forced expiratory volume in the first second) in addition to cell and tissue damage20. Consequently, systemic lung injury due to oxidative stress developed by radiation applied to an extrathoracic region is to be expected. To our knowledge, in the literature, no study has investigated these effects. In this regard, our study focused on the systemic toxic effect of cranial radiation on the lung.
As the lungs are the central organs of the respiratory system and are open to infectious pathogens, metastases, and the toxic effects of radiation in cancer patients, and given that lung complications are fatal and the second most common cause of death in cancer patients 5, new lung protective strategies in patients receiving radiotherapy become necessary.
In our study, high levels of LOOH and TOS, in addition to low levels of TAS and total thiol in the lung after cranial radiation, showed that the lungs were significantly affected by radiation outside the thoracic region.
Many studies have proven the antioxidant, anti-inflammatory, antifibrogenic, antitumor, immunomodulatory, and antimicrobial effects of propolis(6–10). However, in the literature, no study has investigated the systemic radioprotective effects of propolis on lung tissue through oxidative stress mechanisms. To the best of our knowledge, this study is also the first to demonstrate this effect.
There are many available natural or synthetic antioxidant therapeutics to deal with oxidative stress, which act as immunomodulators but at a relatively high cost, such as N-acetyl cysteine, vitamins C, E, A, and beta carotenes21. However, considering the limited effects and costs of these products, propolis, which is a product with high nutritional value and low cost and proven multipotent beneficial effects in many physiologic and pathological conditions, may stand out in lung protective strategies.
In our study, we found that the level of oxidative stress markers in the propolis-treated irradiated group was lower than that in the irradiation alone group but similar to that in the control group. Moreover, the antioxidative markers were similar to those in the control group but higher than those in the irradiation alone group. These facts showed that the systemic oxidative stress in the lungs of cancer patients receiving cranial radiotherapy was adequately suppressed. Consolidation of this efficacy with evidence from larger studies in the future may make propolis a natural combination option in radiotherapy modalities. The lack of a similar study before and the use of a limited number of rat groups are important limitations of our study.
In conclusion, the current study has shown that oxidative stress in the lungs as a systemic toxic effect secondary to cranial irradiation was controlled by propolis. In this regard, it was thought that propolis could be added to radiotherapy modalities as a treatment option due to its protective effect on the lung.