The present study was undertaken to evaluate the effects of a selective thromboxane synthetase inhibitor (OKY-046) on urinary prostaglandins (PGs) excretion and renal parameters such as endogenous creatinine clearance rate (Ccr) and urinary protein excretion in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were divided into two groups; one fed standard chow (DM1) and the other, standard chow mixed with 0.1% OKY-046 (DM2) for 24 weeks. Male Wistar rats were fed standard chow for 24 weeks as control (C). Urinary thromboxane B2 (TXB2) and 6-keto-PGF1α excretions significantly increased in STZ-induced diabetic rats (DM1 and DM2) compared with C after 24 weeks. The increased urinary TXB2 excretion in DM2 was significantly reduced (p < 0.05) compared with that in DM1 (261.1 ± 18.6 ng/gCr versus 380.0 ± 48.4 ng/gCr, mean ± SEM). No significant difference could be found in urinary protein excretion between DM1 and DM2, which was significantly higher in both diabetic groups than C after 12 and 24 weeks. Ccr in both DM1 and DM2 significantly increased (p < 0.05) compared with C after 12 weeks. In contrast, after 24 weeks, Ccr in DM1 fell down to 0.18 ± 0.02 mL/min 100 g body weight (BW), thus being significantly lower (p < 0.05) than that in C (0.27 ± 0.03 mL/min 100 g BW) and DM2 (0.25 ± 0.02 mL/min 100 g BW). Electron microscopic findings in diabetic rats after 24 weeks were the typical change of early diabetic nephropathy, whereas there were no obvious differences between DM1 and DM2. From these results, increased thromboxane A2 from renal origin (partly platelet origin) in STZ-induced diabetic rats appears quite likely to be involved in the pathogenesis of diabetic nephropathy, and the inhibition of TXA2 synthesis by OKY-046 was shown capable of preventing deterioration of renal function.
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism