A poly (ADP-Ribose) polymerase inhibitor ameliorates inflammation associated with diabetic nephropathy

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. The role for PARP in diabetic nephropathy, a devastating complication of diabetes, has not been properly explored. In our previous studies, we have shown that pharmacological inhibition of PARP prevents urinary albuminuria, one of the key manifestations of diabetic kidney disease. The purpose of the current study is to assess the effect of PARP inhibitors on other endpoints of diabetic nephropathy, and, in particular, on variables that characterize renal inflammation. Control and streptozotocin-diabetic rats were treated with or without the PARP inhibitor, 1,5-isoquinolinediol (ISO, 3 mg kg body weight ^-1 d ^-1, intraperitoneally). The inhibitor was administered for ten weeks after two initial weeks without treatment. At the end of the study, concentrations of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNFα) were assessed in the kidney cortex samples of experimental groups. The measures of kidney function and, in particular, urinary total protein and TNFα have also been evaluated.