We examined the protective effect of inositol hexasulfate (IS
6) against tobramycin (TOB)-induced nephrotoxicity. In the electrophoretic analysis, TOB alone and IS
6 alone were observed as single spots on the cathode and anode sides, respectively. However, in the mixture of TOB and IS
6 preincubated at 37°C for 3 hr, the tailing of the spots of TOB and IS
6 were observed from the origin to the cathode and the anode sides, respectively, and the overlapping of the spots of TOB and IS
6 was recognized at the origin. These results indicated that TOB directly interacted with IS
6 in vitro. Assay of TOB binding to rat kidney brush border membranes (BBMs) indicated that IS
6 inhibited the binding of TOB to BBMs through an interaction of TOB and IS
6. No significant reduction in intrarenal TOB level was observed in the rats given TOB (90 mg/kg, s.c.) and IS
6 (153 or 610 mg/kg, s.c.). However, the treatment of rats with a combination of TOB and IS
6 reduced the degree of necrosis of renal tubular cells and also suppressed the increases in urinary protein, urinary enzyme activities, blood urea nitrogen and plasma creatinine induced by TOB. Additionally, we detected a complex of TOB and IS
6 in the urine of rats given both compounds simultaneously. These results indicate that IS
6 protects against TOB-induced nephrotoxicity and that the protective action of IS
6 may be due to the inhibition of TOB binding to BBMs through an interaction of TO B with IS
6.
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