title: Fenofibrate and dipyridamole treatments in low-doses either alone or in combination blunted the development of nephropathy in diabetic rats.
abstract: Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins. Hematoxylin-eosin, periodic acid Schiff and Masson trichrome staining confirmed renal pathological changes in diabetic rats that included glomerular capsular wall distortion, mesangial cell expansion, glomerular microvascular condensation, tubular damage and degeneration and fibrosis. Low-dose fenofibrate (30mg/kg, p.o., 4 weeks) and low-dose dipyridamole (20mg/kg, p.o., 4 weeks) treatment either alone or in combination considerably reduced renal structural and functional abnormalities in diabetic rats, but without affecting the elevated glucose level. Fenofibrate, but not dipyridamole, significantly prevented the lipid alteration and importantly the uric acid elevation in diabetic rats. Lisinopril (5mg/kg, p.o., 4 weeks, reference compound), prevented the hyperglycemia, lipid alteration and development of diabetic nephropathy. Lipid alteration and uric acid elevation, besides hyperglycemia, could play key roles in the development of nephropathy. Low-doses of fenofibrate and dipyridamole treatment either alone or in combination markedly prevented the diabetes-induced nephropathy. Their combination was as effective as to their individual treatment, but not superior in preventing the development of diabetic nephropathy.
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia. Electronic address: pbala2006@gmail.com.
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Rajavel
authors.initials: R
authors.lastname: Varatharajan
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Ying Hui
authors.initials: YH
authors.lastname: Nyo
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Raja
authors.initials: R
authors.lastname: Renushia
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Devarajan
authors.initials: D
authors.lastname: Raaginey
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Ann Nah
authors.initials: AN
authors.lastname: Oh
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Shaikh Sohrab
authors.initials: SS
authors.lastname: Akhtar
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Mani
authors.initials: M
authors.lastname: Rupeshkumar
authors.affiliation: Pharmaceutical Chemistry Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Karupiah
authors.initials: K
authors.lastname: Sundram
authors.affiliation: Pharmaceutical Technology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Sokkalingam A
authors.initials: SA
authors.lastname: Dhanaraj
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004176:Dipyridamole / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D001786:Blood Glucose; D008075:Lipoproteins, HDL; D020011:Protective Agents; D014280:Triglycerides; D014527:Uric Acid; D004176:Dipyridamole; D014508:Urea; D002784:Cholesterol; D003404:Creatinine; D017706:Lisinopril; D011345:Fenofibrate
keywords: Diabetes mellitus; Lipid alteration; Low-dose dipyridamole; Low-dose fenofibrate; Nephropathy; Uric acid elevation