Biochemistry Division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Fundam Clin Pharmacol. 2022 Oct;36(5):801-810. doi: 10.1111/fcp.12781. Epub 2022 May 23.
Pentosan polysulfate sodium (PPS) is a polysulfated glycosaminoglycan approved for the treatment of interstitial cystitis. It also showed renoprotective effects in chronic kidney injury models, for example, 5/6 nephrectomy and diabetic nephropathy (DN). In the present study, we addressed to evaluate the therapeutic value of PPS in DN of rats in combination with losartan (LSR). Sixty male Sprague-Dawley rats were randomly divided into six groups: control group, untreated diabetic groups (8 and 16 weeks after diabetes induction by streptozotocin "STZ", 60 mg/kg, intraperitoneal [I.P.]), LSR-treated diabetic group (10 mg/kg/day, P.O.), PPS-treated diabetic group (25 mg/kg/day, P.O.), and combination-treated diabetic group. Drug treatment was started 8 weeks after induction of diabetes and continued for a further 8 weeks. Renal functions, albuminuria, renal IL-6, oxidative stress, and renal histopathology were evaluated. STZ-treated diabetic rats developed progressive albuminuria, renal dysfunction, and significant glomerular change 16 weeks after induction of diabetes. Administration of PPS, alone or in combination with LSR, showed some beneficial effects on DN evolution and significantly decreased renal inflammation as detected by IL-6 level. The best beneficial effect on DN evolution was obtained by PPS sole therapy based on albuminuria evaluation and renal histopathology. However, the combination of PPS and LSR did not show additive benefits. This study reported that the renoprotection of PPS in the setting of DN is evident by exerting anti-inflammatory and antioxidant effects, but this effect could be masked when combined with an angiotensin receptor blocker.
戊聚糖多硫酸酯钠（PPS）是一种硫酸化糖胺聚糖，已被批准用于治疗间质性膀胱炎。它在慢性肾损伤模型中也表现出肾脏保护作用，例如 5/6 肾切除术和糖尿病肾病（DN）。在本研究中，我们评估了 PPS 与氯沙坦（LSR）联合治疗大鼠 DN 的治疗价值。60 只雄性 Sprague-Dawley 大鼠随机分为六组：对照组、未治疗的糖尿病组（糖尿病诱导后 8 周和 16 周，用链脲佐菌素“STZ”，60mg/kg，腹腔内[I.P.]）、LSR 治疗的糖尿病组（10mg/kg/天，P.O.）、PPS 治疗的糖尿病组（25mg/kg/天，P.O.）和联合治疗的糖尿病组。药物治疗在糖尿病诱导后 8 周开始，并持续 8 周。评估了肾脏功能、蛋白尿、肾脏白细胞介素-6、氧化应激和肾脏组织病理学。STZ 处理的糖尿病大鼠在糖尿病诱导后 16 周时出现进行性蛋白尿、肾功能障碍和明显的肾小球变化。单独或联合 LSR 给予 PPS 显示对 DN 演变有一些有益的影响，并通过白细胞介素-6 水平显著降低肾脏炎症。基于蛋白尿评估和肾脏组织病理学，PPS 单独治疗对 DN 演变的最佳有益作用。然而，PPS 和 LSR 的联合并未显示出附加的益处。本研究报道，PPS 在 DN 中的肾脏保护作用通过发挥抗炎和抗氧化作用是明显的，但当与血管紧张素受体阻滞剂联合使用时，这种作用可能被掩盖。
