title: Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy.
abstract: 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.
authors.affiliation: Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa 125 055, India.
authors.forename: Supriya
authors.initials: S
authors.lastname: Kadian
authors.forename: Nanjaian
authors.initials: N
authors.lastname: Mahadevan
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D013858:Thiobarbiturates / Q000378:metabolism; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D008055:Lipids; D013858:Thiobarbiturates; D003404:Creatinine; D005978:Glutathione; C029684:thiobarbituric acid; D011345:Fenofibrate