Aminoguanidine alleviates radiation-induced small-bowel damage through its antioxidant effect.

Abstract

To evaluate the effect and its mechanism of aminoguanidine (AG) on small-bowel protection after whole-abdominal irradiation (WAI) in rats. 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. 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. 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.