Mycophenolate mofetil ameliorates nephropathy in the obese Zucker rat.
BACKGROUND
The obese Zucker rat has metabolic condition resembling type II diabetes, including hyperlipidemia, obesity, insulin resistance, and hyperglycemia. With advancing age, the obese Zucker rat develops glomerulosclerosis, proteinuria, and renal failure. Since immune cells play a central role in the development of chronic renal injury, we evaluated the potential benefit of mycophenolate mofetil (MMF), alone and in combination with angiotensin receptor type 1 blockade (ARB) in the obese Zucker rat.


METHODS
Thirteen-week-old male obese Zucker rats (fa/fa) were randomly assigned to four experimental groups (five rats each) that received the following treatments for 3 months: (1) losartan (100 mg/L in the drinking water), (2) MMF (20 mg/kg/day), (3) MMF and losartan, and (4) placebo. Lean Zucker rats (N = 5) were included as normal controls. Renal function, biochemical parameters, renal histology, and immunohistology were evaluated.


RESULTS
The placebo-treated obese Zucker rats exhibited proteinuria and significant glomerular and tubulointerstitial injury in association with renal immune cell infiltration. Proteinuria, histologic damage, and renal immune cell infiltration were all reduced by MMF treatment alone or in combination with ARB. The improvement of proteinuria and structural damage was more pronounced in the group that received the combination of MMF and losartan.


CONCLUSIONS
MMF treatment alone, and especially in combination with ARB, improves nephropathy in the obese Zucker rat.
Rodríguez-Iturbe
Bernardo
B
Renal Service, Hospital Universitario, Universidad del Zulia, Instituto de Investigaciones Biomédicas (INBIOMED) Maracaibo, Venezuela. bernardori@telcel.net.ve
Quiroz
Yasmir
Y
Shahkarami
Ashkan
A
Li
Zhen
Z
Vaziri
Nosratola D
ND
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004359:Drug Therapy, Combination; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D009765:Obesity / Q000150:complications*; D051381:Rats; D011924:Rats, Zucker
D047228:Angiotensin II Type 1 Receptor Blockers; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D019808:Losartan