Graduate Thesis Or Dissertation
 

Aminoglycoside nephrotoxicity in rainbow trout (Salmo gairdneri)

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/js956j399

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  • 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 animal mode for investigating the nephrotoxic potential of these agents. Logit analysis revealed that 8-12 day i.p. LD 50's in rainbow trout for TBM and NTM were 53 mg/kg ± 1 mg/kg and 55 mg/kg ± 1 mg/kg respectively (95% c. i.); a no effect dose in rats. Kidney sections from treated animals showed moderate to severe dose-dependent proximal tubular necrosis in both groups, suggesting death of the trout as a consequence of renal failure. NTM caused a greater incidence of glomerular lesions than did TBM. Kidney sections taken one month after a single injection of TBM showed active proximal tubular necrosis suggesting a high binding affinity of these agents for renal tissue. Investigations with transected, catheterized trout given single i.p. injections of 15 or 30 mg/kg TBM or NTM revealed that the earliest and most sensitive indicators of nephrotoxicity were decreases in glomerular filtration rate and proximal tubule secretory ability. This was measured by a decreased clearance of ³H methoxyinulin and ¹⁴C PAH, as compared to saline controls. This was followed by decreased urine flow, and increased urine osmolality and proteinuria. Renal function indices showed the greatest difference from controls at 30 hrs., while histology showed the greatest damage between days 5 and 7. Susceptibility to nephrotoxicity may reflect the individual's ability to effectively compensate for the drug induced drop in renal function. Injection i.v. of the heavy metal positive control cisplatin caused lethality (16.7%) at 2 mg/kg, an approximate human therapeutic dose. Results from this study indicate that the rainbow trout may serve as a sevsitive animal model to study the nephrotoxicity of select therapeutic agents.
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