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

Aim: In this study, we aimed to determine possible mitigation of radiationinduced 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 reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol. Objective: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. Methods: 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 and Conclusion: 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 the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

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Protective Effect of Metformin, Resveratrol and Alpha-lipoic Acid on Radiation- Induced Pneumonitis and Fibrosis: A Histopathological Study

Current Drug Research Reviews ◽

10.2174/2589977511666191018180758 ◽

2019 ◽

Vol 11 (2) ◽

pp. 111-117

Author(s):

Rasoul Yahyapour ◽

Peyman Amini ◽

Hana Saffar ◽

Elahe Motevaseli ◽

Bagher Farhood ◽

...

Keyword(s):

Lipoic Acid ◽

Gamma Ray ◽

Morphological Changes ◽

Inflammatory Cells ◽

Histopathological Study ◽

Alpha Lipoic Acid ◽

Mitochondrial Ros ◽

Antioxidant Defense Enzymes ◽

Radiation Induced ◽

Higher Doses

Background: Radiation-induced pneumonitis and fibrosis are the most common side effects of chest radiotherapy. They result from massive and chronic production of Reactive Oxygen Species (ROS), inhibition of antioxidant enzymes as well as the release of several inflammatory mediators. In this study, we aimed to detect the radioprotective effects of metformin (as inhibitor of mitochondrial ROS), resveratrol (as stimulator of antioxidant defense enzymes) and alpha-lipoic acid (as direct antioxidant) for alleviating radiation-induced pneumonitis and fibrosis. Methods: 80 Male Mice were randomly allotted to eight groups which include G1: control; G2: resveratrol; G3: alpha-lipoic acid; G4: metformin; G5: radiation; G6: radiation plus resveratrol; G7: radiation plus alpha-lipoic acid; G8: radiation plus metformin. Drugs’ doses were as follows: 100 mg/kg metformin, 200 mg/kg resveratrol and 200 mg/kg alpha-lipoic acid. Irradiation with a single radiation dose of 18 Gy was performed using a cobalt-60 (60Co) gamma-ray source. After 80 days, all mice were sacrificed and their lung tissues evaluated for morphological changes using histopathological markers. Results: Irradiation led to acute pneumonitis including infiltration of inflammatory cells and damages to alveolar and vascular, as well as mild fibrosis. Metformin, alpha-lipoic acid and resveratrol were able to reduce pneumonitis and overcome radiation-induced fibrosis. Conclusion: All agents could protect against radiation-induced lung injury moderately. It is possible that administering higher doses of these drugs over a long period of time could give better radioprotection of the lung.

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Mitigation of Radiation-Induced Gastrointestinal System Injury by Melatonin: A Histopathological Study

Current Drug Research Reviews ◽

10.2174/2589977511666191031094625 ◽

2020 ◽

Vol 12 (1) ◽

pp. 72-79

Author(s):

Hossein Sadeghi ◽

Hamed Bagheri ◽

Babak Shekarchi ◽

Abdolreza Javadi ◽

Masoud Najafi

Keyword(s):

Gamma Ray ◽

Radiation Treatment ◽

Cell Damage ◽

Gastrointestinal System ◽

Whole Body ◽

Histopathological Study ◽

Radiation Toxicity ◽

Melatonin Treatment ◽

Gastrointestinal Injury ◽

Radiation Induced

Aims : The current study aimed to investigate the potential role of melatonin in the mitigation of radiation-induced gastrointestinal injury. Background: Organs of the gastrointestinal system such as the intestines, colon, duodenum, ileum etc. are sensitive to ionizing radiation. Mitigation of radiation-induced gastrointestinal injury is an interesting topic in radiobiology and a life-saving approach for exposed persons after a radiation event or improving the quality of life of radiotherapy patients. Methods: 40 male mice were randomly assigned into four groups namely G1: control, G2: melatonin treatment, G3: whole-body irradiation, and G4: melatonin treatment after whole-body irradiation. A cobalt-60 gamma-ray source was used to deliver 7 Gy to the whole body. 100 mg/kg melatonin was administered orally 24 h after irradiation and continued for 5 days. Thirty days after irradiation, histopathological evaluations were performed. Results: The whole-body irradiation led to remarkable inflammation, villi shortening, apoptosis and damage to goblet cells of the small intestine. Furthermore, moderate to severe inflammation, apoptosis, congestion, crypt injury and goblet cell damage were reported for the colon. Treatment with melatonin after whole-body irradiation led to significant mitigation of radiation toxicity in both small and large intestines. Conclusion: Melatonin could mitigate intestinal injury following whole-body exposure to radiation. Treatment with melatonin after an accidental exposure to radiation may increase survival via mitigation of damages to radiosensitive organs, including the gastrointestinal system.

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Evaluating the protective effect of resveratrol, Q10, and alpha-lipoic acid on radiation-induced mice spermatogenesis injury: A histopathological study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v17i12.5791 ◽

2019 ◽

Cited By ~ 1

Author(s):

Masoud Najafi ◽

Mohsen Cheki ◽

Peyman Amini ◽

Abdolreza Javad ◽

Dheyauldeen Shabeeb ◽

...

Keyword(s):

Protective Effect ◽

Lipoic Acid ◽

Coenzyme Q10 ◽

Leydig Cells ◽

Natural Antioxidants ◽

Seminiferous Tubules ◽

Histopathological Study ◽

Alpha Lipoic Acid ◽

Sperm Density ◽

Radiation Induced

Background: Testis is one of the most sensitive organs against the toxic effect of ionizing radiation. Exposure to even a low dose of radiation during radiotherapy, diagnostic radiology, or a radiological event could pose a threat to spermatogenesis. This may lead to temporary or permanent infertility or even transfer of genomic instability to the next generations. Objective: In this study, we evaluated the protective effect of treatment with three natural antioxidants; resveratrol, alpha lipoic acid, and coenzyme Q10 on radiation-induced spermatogenesis injury. Materials and Methods: 30 NMRI mice (6-8 wk, 30 ± 5 gr) were randomly divided into six groups (n=5/each) as 1) control; 2) radiation; 3) radiation + resveratrol; 4) radiation + alpha lipoic acid; 5) radiation + resveratrol + alpha lipoic acid; and 6) radiation+ Q10. Mice were treated with 100 mg/kg resveratrol or 200 mg/kg alpha lipoic acid or a combination of these drugs. Also, Q10 was administered at 200 mg/kg. All treatments were performed daily from two days before to 30 min before irradiation. Afterward, mice were exposed to 2 Gy 60Co gamma rays; 37 days after irradiation, the testicular samples were collected and evaluated for histopathological parameters. Results: Results showed that these agents are able to alleviate some toxicological parameters such as basal lamina and epididymis decreased sperm density. Also, all agents were able to increase Johnsen score. However, they could not protect against radiation-induced edema, atrophy of seminiferous tubules, and hyperplasia in Leydig cells. Conclusion: This study indicates that resveratrol, alpha-lipoic acid, and Q10 have the potential to reduce some of the side effects of radiation on mice spermatogenesis. However, they cannot protect Leydig cells as a source of testosterone and seminiferous tubules as the location of sperm maturation. Key words: Radiation, Spermatogenesis, Resveratrol, Alpha-Lipoic Acid, Coenzyme Q10.

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Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523018666190718161928 ◽

2020 ◽

Vol 19 (2) ◽

pp. 180-189 ◽

Cited By ~ 2

Author(s):

Masoud Najafi ◽

Mohsen Cheki ◽

Gholamreza Hassanzadeh ◽

Peyman Amini ◽

Dheyauldeen Shabeeb ◽

...

Keyword(s):

Whole Body ◽

Gastrointestinal Disorders ◽

Histopathological Study ◽

Radiation Toxicity ◽

Pharmaceutical Treatment ◽

Tissue Samples ◽

Melatonin Administration ◽

Male Wistar Rats ◽

Radiation Induced ◽

High Doses

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

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