Abstract
Effects of tobramycin (TOB) alone and in combination with latamoxef (LMOX) on the stability of rat kidney lysosomal membranes were investigated. Rats were injected with doses of TOB (90 mg/kg/day, s.c.) alone, LMOX (2, 000 mg/kg/day, s.c.) alone or TOB (90 mg/kg/day, s.c.) and LMOX (2, 000 mg/kg/day, s.c.) for 5 consecutive days. The rat kidney lysosomes were isolated on the 1 st, 3rd and 5th days and incubated in a 0.25 M sucrose solution containing 1 mM EDTA (pH 7.0) at 37°C for 20 min. After incubation, the activity of N-acetyl-β-D-glucosaminidase (NAG) released from lysosomes was measured, and the percent NAG release was calculated as an index of the stability of lysosomal membranes. The percent releases of NAG from lysosomes of TOB alone-treated rats were 40 and 50% greater than those of normal rats on the 1st and 3rd days, respectively. On the other hand, treatment with TOB and LMOX suppressed the NAG release from lysosomes with TOB alone by about 80 to 100%. There were insignificant slight increases in the percent NAG release in LMOX alone-treated rats on the 3rd and 5th days. In addition, the in vitro study indicated that incubation of the lysosomal fraction from kidneys of normal rats with TOB (30 μg/ml) significantly increased the NAG release, compared with that of the non-treated lysosomal fraction. However, the preincubated mixture of TOB (30 μg/ml) and LMOX (50 μg/ml) in vitro significantly suppressed the release of NAG from Iysosomes by 85%. These results suggest that the suppression of the releases of NAG from lysosomes by the combination of TOB with LMOX may contribute to the protective effect of LMOX against TOB nephrotoxicity.
