Poly(ADP-ribose) polymerase inhibitor counteracts albuminuria in diabetic rats

Albuminuria, protein albumin present in one's urine, is indicative of kidney dysfunction and is one of the markers of kidney disease in patients with diabetes mellitus. Evidence for the key role of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in chronic diabetic complications in the heart, retina, and peripheral nerves is emerging. This study investigated the effects of the PARP inhibitor 1,5-isoquinolinediol (ISO) on albuminuria in rats that have been made diabetic with streptozotocin (N = 31). ISO (3 mg/kg body weight^-1 d^_1, intraperitoneally) was administered for 10 weeks after two initial weeks without treatment. ISO did not have any effect on weight gain or blood glucose concentrations in either non-diabetic or diabetic rats. At the end of the study, body weights were similarly reduced and blood glucose concentrations similarly increased in untreated and ISO-treated diabetic rats compared with non-diabetic controls. However, the ISO-treated diabetic group showed a significant decrease in consumed water and urination compared with untreated diabetic group (P<.01). Most importantly, ISO treatment reduced urinary albumin excretion to the levels present in non-diabetic rats (P<.01 compared with untreated diabetic group). In conclusion, our study indicates that PARP inhibition is associated with a beneficial effect on urinary albumin excretion, a key marker of diabetic kidney disease. Our findings suggest an important role for PARP in diabetic nephropathy. Studies of other markers of diabetic kidney disease in the streptozotocin-diabetic rat model are in progress.