Amelioration of Diabetic Nephropathy in OLETF Rats by Prostaglandin I₂ Analog, Beraprost Sodium

Abstract

Background: Strict control of blood glucose and blood pressure levels sometimes fails to delay the development of diabetic nephropathy, and an effective therapy is not yet available. The present study aimed to examine whether the prostaglandin I₂ analog beraprost sodium (BPS) ameliorates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Method: Fifty-week-old OLETF rats were divided into three groups according to treatment; 400 μg/kg body weight (BW) BPS, 200 μg/kg BW BPS, and 0.9% saline administration. Kidney histology, index of glomerulosclerosis, and glomerular volume were determined, and urine and serum chemistry were assessed. Results: The values for urine protein excretion and serum blood urea nitrogen in BPS-treated rats were significantly lower than those in untreated rats. In rats treated with 400 μg/kg BW BPS, neither sclerotic changes nor inflammatory cell infiltration were observed. Index of glomerulosclerosis and glomerular volume were also significantly reduced compared with untreated rats. Intriguingly, BPS reduced the level of serum triglyceride. In the glomerulus of treated rats, advanced glycation end product formation and macrophage influx were suppressed in a dose-dependent manner. Conclusion: These findings indicate that BPS has a therapeutic effect on diabetic nephropathy in the OLETF rat, which suggests a potential application of this drug in the treatment of human diabetic nephropathy.

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

“…Second, a small amount of DGLA can be converted to prostacyclin (PGI2) and prostaglandin E1 (PGE1) by δ-5 desaturases. Because PGI2 and PGE1 inhibit platelet aggregation, and PGI2 analogue abrogates glomerular hyperfiltration and macrophage infiltration in diabetic kidneys,35 the effect of GLA may be in part attributed to these consequences. Third, 15-HETE markedly inhibits the generation of leukotriene, which is a potent pro-inflammatory mediator, via stimulating adhesion molecule expression and macrophage infiltration 36.…”

Effects of beraprost sodium on renal function and inflammatory factors of rats with diabetic nephropathy

“…Antioxidants and vasoactive substances are able to enhance the body's antioxidant capacity by reducing the production of free radicals and directly quenching the radicals. A variety of antioxidants such as vitamins C and E, lipoic acid, and vasoactive substances such as BPS have a beneficial effect on the complications of diabetic patients (Watanabe et al, 2009).…”

The urinary levels of prostanoid metabolites predict acute kidney injury in heterogeneous adult Japanese ICU patients: a prospective observational study

“…Prostacyclindeficient mice with a genetic disruption in prostaglandin I 2 synthetase (PGIS) develop renal fibrosis and arterial sclerosis [8], suggesting its involvement in the maintenance of a normal kidney structure. In addition, the renoprotective effects of prostacyclin and its analogs have been reported in various experimental models, including gentamycin-induced tubular injury [9], diabetic nephropathy [10][11][12] and unilateral ureteral obstruction [13,14]. In contrast, thromboxane A 2 (TXA 2 ) exerts effects opposite to those of PGI 2 , in association with the development of vascular lesions [7].…”