Renal protective effect of equol on type 2 diabetic rats

Objective To investigate the effect of equol (Eq) on oxidative stress and inflammatory factors in renal tissue in type 2 diabetes mellitus (T2DM) rats, and explore the possible mechanism in the process. Methods Fifty SD rats aged 6 weeks were selected, and 40 of them were given high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin to establish T2DM rat model, and finally 34 out of 40 were successfully modeled. The rats from the control group (n=10) was fed with ordinary diet, and the T2DM rats were further divided into model group (n=9), and low-(n=9), medium-(n=8) and high-dose (n=8) Eq intervention groups (gavage intervention of 20, 40 and 80 mg/kg Eq, respectively). After 12 consecutive weeks of intervention, serum creatinine (CREA), blood urea nitrogen (BUN), uric acid (UA), and levels of renal oxidative stress and inflammatory factors were detected in each group of rats. HE and PAS stainings were adopted to reveal the histological changes of renal tissue. Western blotting and RT-PCR were performed to determine the activation or inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in renal tissue. Results As compared with the control group, the serum levels of CREA, BUN and UA were significantly increased in the T2DM model group (P < 0.05), and the levels of oxidative stress and inflammation indicators such as malondialdehyde (MDA) and TNF-α in renal tissue were remarkably elevated as well (P < 0.05). The results of HE and PAS stainings showed increased glomerular volume and mesangial matrix, thickened basement membrane of renal capsule, atrophy of renal tubules and dilation of lumen in the model group. Moreover, the protein and mRNA levels of total Nrf2 and HO-1, as well as the expression of nuclear Nrf2 protein were all greatly reduced (P < 0.05). In comparison with the model group, the serum levels of CREA, BUN and UA in the 3 Eq intervention groups were significantly decreased (P < 0.05), levels of oxidative stress and inflammation indexes in renal tissue were reduced (P < 0.05), and the damage of renal microstructure was notably improved. In addition, the protein and mRNA expression of total Nrf2 and HO-1, and nuclear Nrf2 protein level were obviously enhanced (P < 0.05). There was no statistical difference among Eq intervention groups. Conclusion Eq reduces the levels of oxidative stress and inflammatory factors in the renal tissue of T2DM rats, exerting a protective effect on the kidney, in which Nrf2/HO-1 pathway may play an important role.