Mitigation of Radiation-induced Gastrointestinal System Injury using Resveratrol or Alpha-lipoic Acid: A Pilot Histopathological Study

Abstract

Aim: In this study, we aimed to determine possible mitigation of radiation-induced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid. Background: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole body exposure to radiation. Its side effects are responsible for reducing the quality of life of patients who had undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via recycling of ascorbic acid and alpha-tocopherol. Objective: This study is a pilot investigation of mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. Method: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon. Results: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury. Conclusion: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in small and large intestine. Comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

Immunoregulation by resveratrol; implications for normal tissue protection and tumour suppression

“…An experiment confirmed that all such modulatory effects of resveratrol were able to alleviate radiation‐induced enteritis 192 . Another study demonstrated that protection of the intestine by resveratrol against apoptosis and necrosis induction following ionizing radiation ameliorated infiltration of leukocytes, reduced bleeding and alleviated chronic morphological changes in the duodenum, jejunum, ileum and colon 193 . Resveratrol has also been shown to attenuate secretion of inflammatory cytokines in the ileum and the liver following whole body irradiation 194 .…”

“…192 Another study demonstrated that protection of the intestine by resveratrol against apoptosis and necrosis induction following ionizing radiation ameliorated infiltration of leukocytes, reduced bleeding and alleviated chronic morphological changes in the duodenum, jejunum, ileum and colon. 193 Resveratrol has also been shown to attenuate secretion of inflammatory cytokines in the ileum and the liver following whole body irradiation. 194 One of the important targets in the intestine for resveratrol is NLRP3/inflammasome, by inhibiting which, release of IL-1 in the intestine can be decreased by resveratrol.…”

Radiation Medical Countermeasures and Use of EPR Biodosimetry to Facilitate Effectiveness of Applied Clinical Procedures

“…Several plant products alleviate the injurious effects of acute IR exposure, as demonstrated by a large number of investigations in various animal models using largely endpoints that measure either improved rates of survival or improved functions of specific organ systems. Some of these agents are Sea buckthorn (Hippophae rhamnoides-Hippophae) pulp, polyphenols, lycopene, resveratrol, caffeine, curcumin, and Ginkgo biloba extract [88][89][90][91][92][93][94][95].…”

Protective Potentials of Alpha-Lipoic Acid against Ionizing Radiation-Induced Brain Damage in Rats

“…Some studies have reported a number of various strategies to improve the radiotherapeutic efficacy or ameliorate the ionizing radiation-induced toxicity, including (1) the combination of radiation therapy with other cancer treatment modalities (e.g., surgery or chemotherapy), which the aim of the combined therapy is the enhancement of tumor cell sensitivity to radiation therapy [12,13]; (2) the use of advanced radiation therapy techniques (e.g., stereotactic radiosurgery, stereotactic radiotherapy, intensity-modulated radiation therapy, or image-guided radiation therapy) which can result in a more radiation dose to the tumor without an increase in the radiation dose to the surrounding normal organs [13]; and (3) the use of herbal and natural products as radioprotective and radiosensitizing agents for reducing the radiation therapy-induced toxicity [14][15][16][17][18][19][20][21][22].…”