The effect of doxycicline on glomeruloscleresis in renal ablation model

Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are important in the maintenance of extra cellular matrix. Beneficial effects of MMP inhibitors in renal diseases were reported, but their effect on segmental sclerosis is unknown. The aim of this study is to investigate the effect of doxycycline; a tetracycline group antibiotic and an inhibitor of MMP; in renal ablation nephropathy and to evaluate the levels of MMP-2, 9, TIMP I and II, and collagen type IV which might enlighten the mechanism.Fourteen of the 28 female Wistar albino were 5/6 nephrectomised. Doxycyline were given to seven of the 14 nephroctomised and non nephroctomised animals (40 mg/kg/day total 28 days). After sacrification morphological changes in the glomeruli were evaluated by light microscopy; MMP-9 expression with immunoflourescence; TIMP-2 expression with immunohistochemistry. TIMP-1 and TIMP-2 levels were measured with ELISA; pro and activeMMP-2 and MMP-9 were evaluated with zymography.Glomerulosclerosis scores were decreased in 5/6 nephrectomised rats receiving Doxycycline. Collagen type IV was decreased with increased glomerulosclerosis. Compared with the control group MMP-9 was increased in doxycycline administered group, but proMMP-2 and 9 were decreased. When 5/6 nephrectomised groups were compared, Doxycycline administered group had lower glomerulosclerosis scores and TIMP-2 expression; significantly higher pro and activeMMP-2 levels; and similar levels of proMMP-9 and MMP-9; higher amount of type IV collagen.Doxycycline was found to decrease glomerulosclerosis in ablation nephropathy. It is hard to explain the mechanism by MMP-2 and 9, TIMP-1 and TIMP-2 expression. Investigation of collagen III and other MMP?s may clarify the mechanism.Key Words: Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, doxycycline, renal ablation nephropathy, glomerulosclerosis