Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy
Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy
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DOI：
10.1016/j.ejphar.2012.10.012
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发表时间：
2013-01-05
影响因子：
5
通讯作者：
Balakumar, Pitchai
中科院分区：
文献类型：
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作者：
Kadian, Supriya;Mahadevan, Nanjaian;Balakumar, Pitchai
我们之前已经证明，低剂量非诺贝特治疗有能力预防大鼠糖尿病引起的肾病。我们研究了低剂量非诺贝特（30mg /kg/day p.o o）治疗前和治疗后对糖尿病肾病发病的影响。单次给药链脲佐菌素（STZ, 55 mg/kg i.p）致大鼠糖尿病。对糖尿病肾病的发展进行生化和组织学评估。此外，还评估了血脂和肾脏氧化应激。stz给药8周后，糖尿病大鼠血清肌酐、血尿素氮和微量蛋白尿升高，并引起肾小球-包膜壁扭曲、系膜扩张和肾小管损伤以及肾脏氧化应激，出现明显肾病。非诺贝特（30 mg/kg/天，p.o， 4周）预处理（stz给药后4周）可显著预防糖尿病肾病的发生，而非诺贝特（30 mg/kg/天，p.o， 4周）后治疗（stz给药后8周）效果较差。然而，非诺贝特治疗前后均能有效预防糖尿病大鼠肾脏氧化应激和脂质改变，但预处理效果略好。相反，非诺贝特治疗前后并没有改变糖尿病大鼠的血糖水平升高。由此可见，糖尿病诱导的氧化应激和脂质改变，除了显著的葡萄糖升高外，在糖尿病大鼠肾病的发生中起着不利的作用。低剂量非诺贝特预处理可能是预防糖尿病患者在肾脏疾病诱发风险下发生肾病的潜在治疗方法。然而，低剂量非诺贝特治疗可能对糖尿病患者的既定肾病无效。(c) 2012 Elsevier B.V.版权所有
We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30 mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55 mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed. Diabetic rats after 8 weeks of STZ-administration developed apparent nephropathy by elevating serum creatinine, blood urea nitrogen and microproteinuria, and inducing glomerular-capsular wall distortion, mesangial expansion and tubular damage and renal oxidative stress. Fenofibrate (30 mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30 mg/kg/day p.o., 4 weeks) post-treatment (8 weeks after STZ-administration) was less-effective. However, both pre-and post fenofibrate treatments were effective in preventing diabetes-induced renal oxidative stress and lipid alteration in diabetic rats though the pretreatment was slightly more effective. Conversely, both pre-and post fenofibrate treatments did not alter elevated glucose levels in diabetic rats. It may be concluded that diabetes-induced oxidative stress and lipid alteration, in addition to a marked glucose elevation, play a detrimental role in the onset of nephropathy in diabetic rats. The pretreatment with low-dose fenofibrate might be a potential therapeutic approach in preventing the onset of nephropathy in diabetic subjects under the risk of renal disease induction. However, low-dose fenofibrate treatment might not be effective in treating the established nephropathy in diabetic subjects. (c) 2012 Elsevier B.V. All rights reserved.