Protective effect of asiatic acid on renal oxidative stress and apoptosis in diabetic rats

Abstract

Objective To evaluate the effect of asiatic acid (AA) on renal oxidative stress and apoptosis in streptozotocin (STZ)-induced diabetic rats. Methods After the diabetic models were successfully established by intraperitoneal injection of 65 μg/g STZ, 24 living SD rats were randomly assigned to 4 groups, including diabetes mellitus group (DM group), 10 μg·g-1·d-1 AA group, 20 μg·g-1·d-1 AA group, and 40 μg·g-1·d-1 AA group. Another 6 healthy SD rats were used as normal controls (NC group). At 8 weeks, urinary albumin excretion rate (UAER), blood glucose (BG), blood urea nitrogen (BUN), serum creatinine (SCr), superoxide dismutase (SOD) activity, and malondialdehvde (MDA) level were tested. Apoptotic cells in the kidneys were observed by TdT-mediated dUTP nick end labeling (TUNEL), the expression of poly-ADP-ribose polymerase (PARP) was detected by immunohistochemistry, and the apoptosis-related protein cystein asperate proteinase-3 (Caspase-3) was tested by Western blot. One-way of variance and LSD t test were used for data analysis. Results Compared with the NC group, the levels of UAER, BG, BUN, SCr, and MDA were significantly increased, the activity of SOD was significantly decreased, and the number of apoptotic cells and the expression of PARP and Caspase-3 were significantly increased in DM group (31.0%±5.5% vs 5.0%±1.2%, 3.9±0.5 vs 1.7±0.6, 1.7±0.4 vs 0.4±0.3, respectively; all P<0.01). Compared with DM group, UAER, BUN and SCr were improved, the activity of SOD was significantly increased, the level of MDA was reduced, and the number of apoptotic cells (DM group: 31.0%±5.5%; 10 μg·g-1·d-1 AA group: 20.6%±4.7%; 20 μg·g-1·d-1 AA group: 15.8%±2.6%; 40 μg·g-1·d-1 AA group: 10.3%±3.3%) and the expressions of PARP (DM group: 3.9±0.5; 10 μg·g-1·d-1 AA group: 3.0±0.2; 20 μg·g-1·d-1 AA group: 2.6±0.4; 40 μg·g-1·d-1 AA group: 2.0±0.3) and apoptosis-related protein Caspase-3 (DM group: 1.7±0.3; 10 μg·g-1·d-1 AA group: 1.0±0.2; 20 μg·g-1·d-1 AA group: 0.7±0.2; 40 μg·g-1·d-1 AA group: 0.5±0.3) were reduced in all 3 AA intervention groups. Conclusion AA may play a protective role in STZ-induced diabetic nephropathy, which could be related to the inhibition of oxidative stress and apoptosis. Key words: Diabetic nephropathies; Oxidative stress; Apoptosis; Oxalic acids