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Accepted: October 5, 2000
Key Words
Mesangial cell proliferation * Interleukin-6 * Dilazep
Abstract
Background: Anti platelet agents have been widely used to reduce proteinuria and to prevent the progression of chronic glomerulonephritis or diabetic nephropathy to end-stage renal failure. Dipyridamole, one type of antiplatelet drug, inhibits the proliferation of glomerular mesangial cells (MCs). The effect of dilazep hydrochloride (dilazep) on these cells is still obscure. The effects of dilazep on cultured MC IL-6 secretion and proliferation were investigated in the present study. Methods: IL-6 secretion from MC induced by bacterial lipopolysaccharide (LPS) were assessed using sandwich ELISA. LPS-induced MC proliferation was detected by ^sup 3^H-thymidine incorporation and WST-1 assay (similar to MTT assay).
Results: Incubation of MCs with various dosages of LPS (0, 1, 10, 50 and 100 ng/ml) induced IL-6 secretion in a dose-dependent manner. However, dilazep significantly inhibited this LPS-induced IL-6 secretion from MCs in a close- and time-dependent manner. Dilazep also significantly inhibited MC proliferation in a dose-dependent
manner. Conclusion: It appears that these effects of dilazep may prevent progression of mesangial proliferative glomerulonephritis.
Introduction
The clinical effects of dilazep hydrochloride (dilazep) on the improvement of proteinuria in patients with chronic glomerulonephritis, including IgA nephropathy, nephrotic syndrome and diabetic nephropathy, have mainly been reported in Japan [1,2]. Koide et al. [3] reported that the administration of dilazep from the early stage of diabetic nephropathy may be useful for the improvement of albuminuria and prevention of renal function.
Several pharmacological effects of dilazep have been reported as follows: (1) suppression of platelet adhesion and coagulation; (2) suppression of phospholipase activity of platelets; (3) increase in red blood cell activity; (4) suppression of the decrease in anionic charge in the glomerular basement membrane, and (5) maintenance of glomerular filtration rate due to increased renal blood flow [4, 5]. Although dipyridamole [6,7], another type of antiplatelet drug, inhibits glomerular mesangial cell (MC) proliferation, the inhibition of MC proliferation of dilazep remains unclarified.
The purpose of the present study is to investigate the effect of dilazep on IL-6 secretion from MCs and MC proliferation in vitro.
Materials and Methods
Cytotoxicic Activity
To exclude the toxic effect of dilazep on MC, the cytotoxic activity was examined using 2 methods, i.e. WST-1...