Effects of semicarbazide-sensitive amine oxidase inhibitors on morphology of aorta and kidney in diabetic rats

Background The present study aimed to investigate the inhibitory effects of aminoguanidine (AG) and 2-bromoethylamine (2-BEA) on the semicarbazide-sensitive amine oxidase (SSAO) activity both in vitro and in vivo, and the prevention role of AG and 2-BEA in the morphology of aorta and kidney in diabetic rats. Methods The aortic homogenates isolated from Sprague-Dawley (SD) rats were treated with different concentrations of AG or 2-BEA to investigate the inhibitory effects on the SSAO activity in vitro, using benzylamine as the substrate. In addition, 65 male SD rats were randomly assigned into normal control (NC) (n = 10), NC + AG (n = 10), NC + 2-BEA (n = 10) and diabetes mellitus (DM) model groups (n = 35). Type 1 diabetic rat model was induced by intraperitoneal injection of 1% streptozotocin-sodium citrate buffer 55 mg/kg. After establishing the diabetic rat model by a single intraperitoneal injection of streptozotocin. Except those failed in modeling, 30 rats in the DM model group were further randomly divided into the DM, DM + AG, DM + 2-BEA groups (n = 10 in each). Rats in the DM + AG and NC + AG group were intraperitoneally injected with AG (25 mg/kg),those in the DM + 2-BEA and NC + 2-BEA group were administered with 2-BEA (20 mg/kg) daily for eight weeks. After eight weeks of treatment, the SSAO activity in the plasma and aorta, and plasma levels of formaldehyde (FA) and methylamine (MA) were measured by high performance liquid chromatograph. Radioimmunoassay was used to determine the plasma endothelin-1 (ET-1) concentration, while nitric acid deoxidized enzyme method was performed to detect the plasma nitrate/nitrite (NO(x)-) level. Besides, the morphological changes of aorta and kidney tissues were examined by optical and electron microscopes. Results Both AG and 2-BEA exerted strong inhibitory effect on the aortic SSAO activity in vitro, with the IC50 values of 12.76 μmol/L and 3.83 μmol/L, respectively. Compared with the NC group, the SSAO activity in the plasma and aorta, and plasma levels of MA and ET-1 were significantly increased (P