Radiation‐induced enteritis is one of the greatest challenges in radiotherapy. The current study was designed to evaluate the ameliorative effect of resveratrol, which exhibits anti‐inflammatory property, against radiation‐induced intestinal injury in rats and to explore the underlying mechanism. Rats were exposed to a single dose of 5 Gy. Resveratrol (20 mg/kg/day) was orally administered to irradiated rats over 3 weeks. Results showed that resveratrol ameliorated the intestinal oxidative stress parameters; malondialdehyde (MDA) content, glutathione (GSH) level, and catalase (CAT) activity compared to irradiated group. Furthermore, resveratrol reduced the contents of inflammatory cytokines; tumor necrosis factor α (TNF‐α), nuclear factor‐kappa (NF‐κB), and interleukin 1β (IL‐1β) in intestine. Western blotting analysis revealed that resveratrol down‐regulated the proteins expression of phosphoinositide 3‐kinases (PI3K), protein kinase B (Akt) as well as the mammalian target of rapamycin (mTOR) in intestinal tissues of irradiated rats and thus reduced the inflammatory mediator production. These results were confirmed by histopathological investigation. In conclusion, resveratrol attenuated intestinal inflammation following irradiation via modulating PI3K/Akt/mTOR pathway and thereby could be a promising adjuvant in radiotherapy.

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Cardiovascular disease is one of the most pivotal disorders after radiotherapy. The aim of this study investigates the possible protective effect of metformin against gamma radiation‐induced heart damage in male rats. Group 1 (control) received saline, group 2 was whole body gamma‐irradiated 5 Gy, group 3 was orally administered metformin 50 mg/kg/day for 2 weeks, group 4 received metformin 50 mg/kg/day for 1 week, then exposed to whole‐body gamma radiation at a dose of 5 Gy and continued with metformin for further 1 week. The results revealed that the administration of metformin to irradiated rats significantly ameliorated the changes in cardiac biomarkers (LDH and CK‐MB) compared with irradiated group. Heart catalase and SOD activities showed normal level when compared with the irradiated group. Also, NF‐κB, IL‐6 and TNF‐ α levels were markedly decreased compared with the corresponding values of irradiated group. Consequently, metformin reduced E‐selectin as well ICAM and VCAM‐1. These results confirmed by histopathological examination. In conclusion, concomitant administration of metformin during radiotherapy acts as a potent heart protector from oxidative stress, inflammatory mediators and endothelial dysfunction induced damages. Results thus hold a great promise for a new implication of an antidiabetic drug (metformin) as adjunct to radiotherapy.

The low dose of radiation (LDR) has received growing attention for its beneficial neuroprotective effect. This study was designed to investigate the enhancing effect of LDR on the antidepressant potential of resveratrol against diazepam‐induced depression in mice. Female mice divided into five groups; control, diazepam (2 mg/kg), LDR (0.5Gy) + diazepam, resveratrol (20 mg/kg) + diazepam, LDR + resveratrol+diazepam. Mice received diazepam showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swimming and tail suspension tests integrated with a marked decline in biogenic amines (serotonin, norepinephrine, and dopamine) in brain tissues. These effects were ameliorated by LDR or resveratrol administration demonstrating an antidepressant activity. Interestingly, LDR triggered the antidepressant effect of resveratrol as it restored the changes in behavioral tests, neurotransmitters, and neuro‐histoarchitecture. In conclusion, these findings suggested that LDR could be considered as a novel adjuvant that augmented the resveratrol antidepressant effect and might serve as a potential therapeutic approach for depression.

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