Single-dose aminoglycoside nephrotoxicity and lethality in rainbow trout

Abstract

The nephrotoxicities of the aminoglycoside antibiotics, tobramycin (TBM) and netilmicin (NTM), were studied in rainbow trout ( Salmo gairdneri) to determine the usefulness of salmonids as a sensitive model for investigating the nephrotoxic potential of these agents. Logit analysis revealed that 8 to 12-day ip LD50s in rainbow trout for TBM and NTM were 53 ± 1 and 55 ± 1 mg/kg, respectively (95% c.i.), a nonobserved effect dose in rats. Kidney sections from treated animals showed moderate to severe dose-dependent proximal tubular necrosis in both groups, suggesting that lethality was a consequence of renal failure. NTM caused a greater incidence of glomerular lesions than did TBM. Kidney sections taken 1 month after a single injection of TBM showed active necrosis of proximal tubules suggesting a high affinity of these agents for trout renal tissue. Investigations with spinally transected, catheterized trout given single ip injections of 15 or 30 mg/kg TBM or NTM revealed that the earliest and most sensitive indicators of nephrotoxicity were decrease in clearance of [ 3H]methoxyinulin and p-[ 14C]p-aminohippuric acid. This finding was followed by decreased urine flow, increased urine osmolality, and proteinuria. Renal function indices showed the greatest difference from controls at 30 hr, while morphologic damage was greatest between Days 5 and 10. Physiological and histopathological data indicate that NTM is less toxic than TBM in rainbow trout. Results from this study suggest that the rainbow trout is a sensitive animal model in which to study the nephrotoxicity of aminoglycoside antibiotics.