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Aminoguanidine Alleviates Radiation-Induced Small-Bowel Damage Through Its Antioxidant Effect
- Source :
-
International Journal of Radiation Oncology, Biology, Physics . May2009, Vol. 74 Issue 1, p237-244. 8p. - Publication Year :
- 2009
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Abstract
- Purpose: To evaluate the effect and its mechanism of aminoguanidine (AG) on small-bowel protection after whole-abdominal irradiation (WAI) in rats. Methods and Materials: Male Sprague-Dawley rats (300–400 g) subjected to 12 Gy WAI were used for the study. Aminoguanidine at a dose of 50–800 mg/kg was administered by the gavage route 2 h before WAI. Mucosal damage of small bowel was evaluated by the grade of diarrhea and crypt survival; oxidative stress was determined by the level of 8-hydroxy 2′-deoxyguanosine (8-OHdG) with immunohistochemistry (IHC). Nitrosative stress was evaluated by the expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) with IHC, and systemic and portal vein NOx (nitrite + nitrate) levels were measured and compared with and without AG treatment after WAI. Results: Aminoguanidine showed a dose-dependent effect against WAI-induced diarrhea. Aminoguanidine at a dose of 400 mg/kg had the best protective effect, from 92% to 17% (p = 0.002). Aminoguanidine increased crypt survival from 23% to 46% (p = 0.003). It also significantly attenuated 8-OHdG expression but not 3-NT and iNOS expression at both 4 and 8 h after 12-Gy WAI. Aminoguanidine did not alter the portal vein NOx levels 4 and 8 h after 12-Gy WAI. Conclusion: Aminoguanidine has a radioprotective effect against radiation-induced small-bowel damage due to its antioxidant effect but not inhibition of nitric oxide production. Dietary AG may have a potentially protective effect on the small intestine of patients subjected to pelvic and abdominal radiotherapies. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 03603016
- Volume :
- 74
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- International Journal of Radiation Oncology, Biology, Physics
- Publication Type :
- Academic Journal
- Accession number :
- 37573031
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2009.01.017