Effects of pravastatin or 12/15 lipoxygenase pathway inhibitors on indices of diabetic nephropathy in an experimental model of diabetic renal disease.
OBJECTIVE
To attenuate the effects of early streptozotocin-induced diabetes on renal functions through supplementation with either pravastatin or 12/15-lipoxygenase pathway inhibitors.


METHODS
The study was carried out at King Khalid University Hospital, Riyadh, Saudi Arabia from November 2010 to November 2011. Rats were assigned to control rats (group I) receiving vehicle; normoalbuminuric diabetic rats receiving vehicle (group IIa), nordihydroguaiaretic acid (NDGA) (group IIb), NDGA + insulin (group IIc), pravastatin (group IId) or pravastatin + insulin (group IIe); and microalbuminuric diabetic rats receiving vehicle (group IIIa), NDGA (group IIIb), NDGA + insulin (group IIIc), pravastatin (group IIId) or pravastatin + insulin (group IIIe). The NDGA and pravastatin were administered for 4 months. At the end of the experiment, renal function tests were measured and blood samples were analyzed.


RESULTS
Both NDGA and pravastatin had favorable effects on renal function to the same extent, and more favorable effects when diabetes was controlled. Indices of diabetic nephropathy (DN) and oxidative stress were reduced by NDGA or pravastatin therapy with no statistical difference between the 2 lines of therapy.


CONCLUSIONS
Pravastatin and 12/15-lipoxygenase pathway inhibitor (NDGA) have beneficial effects on streptozotocin-induced DN. The findings may provide insight into the feasibility of their clinical use as a complementary therapy for the prevention/treatment of DN.
Department of Physiology, College of Medicine, King Saud University, PO Box 2925 (29), Riyadh 11461, Kingdom of Saudi Arabia. hayam_gad@hotmail.com
Hayam I
HI
Gad
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001092:Arachidonate 12-Lipoxygenase / Q000187:drug effects; D001093:Arachidonate 15-Lipoxygenase / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000150:complications / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
C475064:12-15-lipoxygenase; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D017035:Pravastatin