Effects of antiplatelet drug dilazep dihydrochloride on anionic sites and extracellular matrix (ecm) components in glomerular basement membrane of stz‐induced diabetic rats

Abstract

A study of anionic sites in the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced diabetic rats with or without treatment by an antiplatelet drug, dilazep dihydrochloride, is described. Expression of glomerular extracellular matrix (ECM) components was examined by immunofluorescence. Renal specimens were immersed in polyethyleneimine (PEI) as a cationic probe and then examined by electron microscopy. Renal specimens were also incubated with rabbit antirat type IV collagen, laminin, and fibronectin antisera and then stained with fluorescein isothiocyanate (FITC)-labeled goat antirabbit IgG antiserum. Mean values of proteinuria in the dilazep-treated diabetic rats were significantly decreased compared with those in nontreated diabetic rats. There was no significant correlation between the levels of proteinuria and those of creatinine clearance (CCr). Number of anionic sites on the GBM in the dilazep-treated diabetic rats were greater than those in diabetic rats. There was no significant difference in the staining of such ECM components between both rat groups. The authors concluded that the dilazep dihydrochloride might prevent anionic charges on the GBM and decrease the urinary excretion of proteins in STZ-induced diabetic rats.

Dilazep, a nucleoside transporter inhibitor, modulates cell cycle progression and DNA synthesis in rat mesangial cells in vitro

“…However, only a few mechanisms have been proposed for the effects of dilazep on diseases of the kidney. These include (a) suppression of the decrease in anionic charge in the glomerular basement membrane ( Yamamoto et al . 1995 ), and (b) suppression of platelet adhesion and coagulation and the maintenance of the glomerular filtration rate as a result of increased renal blood flow ( Nagase et al .…”

“…Dilazep, an antiplatelet agent, is generally used as an antithrombotic drug in clinical practice (Inage et al 1985, Maruhama et al 1985, Tajiri et al 1989, Nakazawa et al 1993, Yamamoto et al 1995. Dilazep is also known to exert cytoprotective and antioxidant effects in some ischaemic heart models (Tanabe et al 1992, Houge et al 1996, Hara & Abiko 1996.…”

“…However, only a few mechanisms have been proposed for the effects of dilazep on diseases of the kidney. These include (a) suppression of the decrease in anionic charge in the glomerular basement membrane (Yamamoto et al 1995), and (b) suppression of platelet adhesion and coagulation and the maintenance of the glomerular ®ltration rate as a result of increased renal blood ¯ow (Nagase et al 1985, Yasunaga et al 1988. The former can improve proteinuria and the latter should suppress mesangial cell proliferation by inhibiting plateletderived growth factor released from platelets (Iida et al 1988, Silver, Jaffer & Abboud 1989, Floege et al 1992.…”

The Role of Platelets in Diabetic Kidney Disease

“…Dilazep hydrochloride prevented glomerulosclerosis and tubular atrophy and reduced positive staining for type IV collagen in the glomeruli of diabetic rats [ 176 ]. Dilazep dihydrochloride also prevented anionic charges on the GBM and decreased the urinary excretion of proteins in STZ-induced diabetic rats [ 213 ].…”