Studies on pyrazinoylguanidine. 5. Temporal effects over 24 weeks demonstrating attenuation of diabetic nephropathy in STZ-diabetic rats.
This study was designed to determine whether pyrazinoylguanidine (PZG) can attenuate diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced within 1 week after a single intraperitoneal dose of STZ (45 mg/kg in 0.05 mol/l sodium citrate buffer). Diabetic rats were divided into five groups. Each group received by gavage for 24 weeks one of the following: vehicle (saline 10 ml/kg, b.i.d.), PZG (35 mg/kg, b.i.d.), captopril (15 mg/kg, b.i.d.), or hydrochlorothiazide (HCTZ, 20 mg/kg, b.i.d.). Insulin (NPH 7.5 U/day) was given subcutaneously. PZG treatment for 24 weeks reduced mortality and attenuated diabetic nephropathy, as indicated by reduced urinary excretion of total protein (79% of control), low-molecular-weight protein (12% of control), and albumin (60% of control). PZG also preserved renal structure and function. Compared to HCTZ or vehicle-treated rats, STZ-diabetic rats receiving either captopril or insulin exhibited decreased excretion of total protein, low-molecular-weight protein, and albumin, as well as amelioration of renal pathology. Collectively, these results indicate that PZG, as well as captopril and insulin, improved longevity and several indices of diabetic nephropathy in STZ-diabetic rats.
Follansbee
M H
MH
Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Beyer
K H
KH
Griffith
J W
JW
Vesell
E S
ES
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D008970:Molecular Weight; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013311:Streptozocin
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006146:Guanidines; D007004:Hypoglycemic Agents; D007328:Insulin; D011719:Pyrazines; D012709:Serum Albumin; D006852:Hydrochlorothiazide; D013311:Streptozocin; C056104:2-pyrazinoylguanidine; D002216:Captopril