Studies on the Nephrotoxicity of Aminoglycoside Antibiotics and Protection from These Effects (3) Protective Effect of Latamoxef against Tobramycin Nephrotoxicity and Its Protective Mechanism

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Abstract
Effect of latamoxef (LMOX) against tobramycin (TOB)-induced nephrotoxicity was studied in rats. Treatment with TOB (90 mg/kg/day, s.c.) alone resulted in marked increases in the activities of urinary enzymes such as lactate dehydrogenase, N-acetyl-.beta.-D-glucosaminidase and lysozyme, urinary protein content and blood urea nitrogen, which peaked on the 7th or 10th day. The combination with LMOX (500, 1000 or 2000 mg/kg/day, s.c.) significantly suppressed increases in the parameters with TOB alone. The extent of this suppression roughly depended on the LMOX dosage. Although TOB alone caused pronounced histological changes such as extensive cortical proximal tubular cell necrosis, residual tubular basement membrane and cast formations in the renal cortex and medulla on the 7th day, these changes were apparently suppressed by combination with LMOX. In addition, intrarenal TOB concentrations in the rat given TOB alone were about 350, 500 and 1000 .mu.g/g tissue wet weight at 3 hr, on day 3 and on day 5, respectively. On the other hand, there was a significant reduction (30-60%) in intrarenal TOB concentration by combination with LMOX. These results indicate that combination with LMOX obviously protects the rat kidney from TOB nephrotoxicity, and the protective effect may be partially due to suppression of intrarenal accumulation of TOB by LMOX.

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