PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation

Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria and renal injury in salt-loaded DS rats with elevated blood pressure, accompanied by renal inflammation suppression. Notably, high salt increased renal expression of active Rac1, followed by increased Sgk1 expressions, a downstream molecule of mineralocorticoid receptor (MR) signal, indicating salt-induced activation of Rac1-MR pathway. However, BPS administration inhibited salt-induced Rac1-MR activation as well as renal inflammation and damage, suggesting that Rac1-MR pathway is involved in anti-inflammatory and renoprotective effects of PGI2. Based upon Rac1 activated by inflammation, moreover, BPS inhibited salt-induced activation of Rac1-MR pathway by renal inflammation suppression, resulting in the attenuation of renal damage in salt-loaded DS rats. Thus, BPS is efficacious for the treatment of salt-induced renal injury.

Combination therapy with beraprost sodium and aspirin for acute ischemic stroke: a single-center retrospective study

Objectives To evaluate the effectiveness and safety of the combination of beraprost sodium (BPS) and aspirin in patients with acute ischemic stroke (AIS). Methods There were 384 patients with AIS enrolled in this single-center, retrospective study. The BPS group comprised patients who received combination therapy with BPS and aspirin, and the control group comprised those who received only aspirin. Primary measurements were glomerular filtration rate (GFR), cystatin-c (Cys-C), National Institute of Health Stroke Scale (NIHSS) score, modified activities of daily living index (MBI), modified Rankin scale (mRS), and blood coagulation indexes. Recurrence and adverse events were recorded. Results There were no significant differences in patient characteristics at baseline between the two groups. GFR and Cys-C levels increased in the BPS group compared with the control group. After treatment, the NIHSS and mRS score were significantly lower in the BPS group compared with the control group, whereas the MBI scores were significantly higher in the BPS group compared with the control group. There was no significant difference in blood coagulation between the two groups. There were no serious adverse events in either group. Conclusions Combination therapy with BPS and aspirin may be a safe and effective treatment for AIS.