Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy

• Published in: European journal of pharmacology Vol. 698; no. 1-3; pp. 388 - 396
• Main Authors: Kadian, Supriya, Mahadevan, Nanjaian, Balakumar, Pitchai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2013
• Subjects: Animals; blood; Blood Glucose; Blood Glucose - metabolism; blood serum; Blood Urea Nitrogen; Body Weight; Body Weight - drug effects; creatinine; Creatinine - blood; Diabetes mellitus; Diabetic Nephropathies; Diabetic Nephropathies - blood; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - pathology; Diabetic Nephropathies - urine; diabetic nephropathy; Dose-Response Relationship, Drug; drug effects; drug therapy; Female; Fenofibrate; Fenofibrate - pharmacology; Fenofibrate - therapeutic use; glucose; Glutathione; Glutathione - metabolism; Hyperglycemia; Kidney; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Lipid alteration; Lipids; Lipids - blood; Low-dose strategy; Male; metabolism; Nephropathy; Organ Size; Organ Size - drug effects; Oxidative stress; pathology; pharmacology; Pre- and post-treatment strategies; Proteinuria; Proteinuria - drug therapy; Rats; Rats, Wistar; risk; streptozotocin; therapeutic use; Thiobarbiturates; Thiobarbiturates - metabolism; Time Factors; urea nitrogen; urine; Fenofibrate; Oxidative stress; Hyperglycemia; Lipid alteration; Nephropathy; Pre- and post-treatment strategies; Diabetes mellitus; Low-dose strategy
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2012.10.012

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 (30mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55mg/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 (30mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30mg/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. [Display omitted]