Aminoguanidine Alleviates Radiation-Induced Small-Bowel Damage Through Its Antioxidant Effect

Huang, Eng‐Yen; Wang, Feng‐Sheng; Lin, I-Hui; Yang, Kuender D.

doi:10.1016/j.ijrobp.2009.01.017

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…Earlier our group also reported significant iNOS inihibition in lung tissues of irradiated mice by our previously derived formulation [18]. In line with our observation, other agents like Aminoguanidine [36], 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG) [37] have been reported for their radioprotective ability in intestine, blood and bone marrow of mice mainly through inhibition of iNOS.…”

Section: Discussionsupporting

confidence: 86%

A Combination of Podophyllotoxin and Rutin Attenuates Radiation Induced Gastrointestinal Injury by Negatively Regulating NF-κB/p53 Signaling in Lethally Irradiated Mice

et al. 2016

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Development of an effective radio protector to minimise radiation-inflicted damages have largely failed owing to inherent toxicity of most of the agents examined so far. This study is centred towards delivering protection to lethally irradiated mice by pre-administration of a safe formulation G-003M (combination of podophyllotoxin and rutin) majorly through regulation of inflammatory and cell death pathways in mice. Single intramuscular dose of G-003M injected 60 min prior to 9 Gy exposure rescued 89% of whole body lethally irradiated C57BL/6J mice. Studies have revealed reduction in radiation induced reactive oxygen species (ROS), nitric oxide (NO) generation, prostaglandin E2 (PGE2) levels and intestinal apoptosis in G-003M pre-treated mice intestine. Restricted nuclear translocation of redox-sensitive Nuclear factor-κB (NF-κB) and subsequent downregulation of cyclo-oxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS; EC 1.14.13.39) and tumor necrosis factor (TNF-α) levels demonstrated the anti-inflammatory effect that G-003M exerts. Support to early hematopoietic recovery was exhibited through G-003M mediated induction of granulocyte colony stimulating factor (G-CSF) and interleukin (IL-6) levels in lethally irradiated mice. Considerable attenuation in radiation induced morphological damage to the intestinal villi, crypts and mucosal layers was observed in G-003M pre-treated mice. Additionally, our formulation did not reduce the sensitivity of tumor tissue to radiation. Altogether, these results suggest that G-003M ameliorates the deleterious effects of radiation exposure by minimising ROS and NO generation and effectively regulating inflammatory and cell death pathways. Mechanism of protection elucidated in the current study demonstrates that G-003M can be used as a safe and effective radio protective agent in radiotherapy for human application.

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Section: Discussionsupporting

confidence: 86%

A Combination of Podophyllotoxin and Rutin Attenuates Radiation Induced Gastrointestinal Injury by Negatively Regulating NF-κB/p53 Signaling in Lethally Irradiated Mice

et al. 2016

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“…The protective effect of AG against ionising radiation has already been shown in rats with whole‐body irradiation with a single dose of 8 Gy using NO‐synthase inhibitors (Babicová et al ., ). Also in recent studies, the therapeutic effect of AG against radiation in rat models has been shown on lungs and small bowels using antioxidant enzymes (Eroglu et al ., ; Huang et al ., ). To the best of our knowledge, there is no study in the literature regarding the use of AG against RT‐induced testis and kidney injury.…”

Section: Discussionmentioning

confidence: 97%

“…Also, AG has a cytoprotective effect via its antioxidant properties in vitro and in vivo . Many studies have reported that AG acts as an antioxidant and prevents the loss of antioxidant enzyme activities and cellular damage in rats (Huang et al ., ; Abo‐Salem, ). For instance, Parlakpinar et al .…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of aminoguanidine on radiotherapy-induced kidney and testis injury

et al. 2015

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This experimental study was designed to investigate both protective and therapeutic effects of aminoguanidine (AG), on radiotherapy (RT)-induced oxidative stress in kidney and testis. Forty rats were divided into five groups equally as follows: (i) control, (ii) RT, (iii) AG, (iv) AG+RT and (v) RT+AG group. Histopathological findings and biochemical evaluations, including tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), total oxidant status (TOS), total antioxidant capacity, oxidative stress index (OSI), blood urea nitrogen (BUN), serum creatinine (Cr) and testosterone levels, were determined. MDA, TOS and OSI were significantly higher in RT-treated groups, whereas SOD, CAT, GPX and GSH were significantly lower in these groups when compared with the control rats in the kidney and testis tissue. AG treatment significantly decreased MDA, TOS and OSI levels and increased SOD, CAT, GPX and GSH levels, when compared to the RT-treated groups in both kidney and testis tissue. BUN and Cr levels did not change among the groups, whereas testosterone levels were found as reduced in the RT-treated rats. AG treatment significantly augmented these hazardous effects of RT on testis tissue. According to our results, AG has beneficial effects against RT-induced kidney and testis injury.

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“…Examinations were performed with future clinical application in mind. Huang et al administered aminoguanidine prior to irradiation when examining the effects of this agent on small bowel damage in rats, to demonstrate its prophylactic effect (8). By contrast, Emami et al administered aminoguanidine after irradiation, with the intention of showing its therapeutic effect (24).…”

Section: Discussionmentioning

confidence: 99%

“…Certain studies have suggested that radiation enterocolitis is caused by oxidative stress, as antioxidants including aminoguanidine, octreotide and glutamine have been shown to improve radiation enterocolitis in animal models (8–10). In this study, a new antioxidant agent, ETS-GS (γ-L-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltri-decyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-oxo-3-[(2-sulfoethyl)amino]propyl]-L-cysteinylglycine sodium salt), was developed for the treatment of radiation enterocolitis.…”

Section: Introductionmentioning

confidence: 99%

Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model

et al. 2013

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Radiation enterocolitis is a severe adverse event that occurs after radiotherapy for malignant abdominal tumors. In this study, the therapeutic effects of ETS-GS, a novel vitamin E derivative with antioxidative and anti-inflammatory abilities, were examined in a rat model of radiation enterocolitis. The radiation enterocolitis model was created by irradiation of male rats with a single dose of 10 Gy. ETS-GS was administered subcutaneously (10 mg/kg/day) for five consecutive days from two days prior to irradiation. The animals were sacrificed three days after irradiation; following which, ileal tissue samples were analyzed for macroscopic and histological findings, presence of apoptosis, degree of oxidative stress and inflammation. In the irradiated group, severe erosion was observed in the small intestine in addition to necrosis of the mucosal layer, swelling and invasion of inflammatory cells of the submucosal layer, and shortening of the crypts. In irradiated rats that received ETS-GS, mucosal injury in the small intestine was milder compared with that of irradiated rats that received no ETS-GS. In addition, ETS-GS decreased apoptosis in the small intestine and reduced the activity of myeloperoxidase and malondialdehyde, which are markers for inflammation and oxidative stress. ETS-GS with antioxidant activity has a therapeutic effect on the symptoms of radiation enterocolitis in a rat model.

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Aminoguanidine Alleviates Radiation-Induced Small-Bowel Damage Through Its Antioxidant Effect

Cited by 19 publications

References 28 publications

A Combination of Podophyllotoxin and Rutin Attenuates Radiation Induced Gastrointestinal Injury by Negatively Regulating NF-κB/p53 Signaling in Lethally Irradiated Mice

A Combination of Podophyllotoxin and Rutin Attenuates Radiation Induced Gastrointestinal Injury by Negatively Regulating NF-κB/p53 Signaling in Lethally Irradiated Mice

Beneficial effects of aminoguanidine on radiotherapy-induced kidney and testis injury

Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model

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