Gentamicin nephrotoxicity is well documented in mammals.(1,2,3) Tubular epithelial cells undergo necrosis and slough into the lumen of the nephron. In cases of sublethal toxicity, the mammalian kidney can regenerate injured nephrons. Surviving epithelial cells flatten, divide and migrate along the denuded basement membrane to reestablish the tubular epithelium. This process begins several days following gentamicin administration, with a regenerated epithelium present in the following weeks.

Gentamicin has been used to treat bacterial infections in fish, especially valuable aquarium species.(4) The pharmacokinetics of gentamicin in channel catfish has been determined.(5) Most clinicians assume that high levels of gentamicin are nephrotoxic in fish. There have been, however, no studies describing the cellular injury or repair of lesions caused by gentamicin in the fish kidney. The present study was conducted to demonstrate the response of the goldfish kidney, Carassius auratus, to a sublethal dose of gentamicin.

Goldfish were given intraperitoneal injections with 50 mg/kg gentamicin. Fish were sacrificed at various times following gentamicin administration. Within 48 hours the proximal tubular epithelium became very eosinophilic and began to undergo necrosis. Nuclei became pyknotic and epithelial cells sloughed into the lumens of the tubules. By one week, a flattened, basophilic epithelium was noted in the injured tubules, indicating regeneration along the nephron. This is similar to what is seen in the mammalian kidney. By two weeks, newly developing basophilic nephrons were observed. These nephrons are only found in embryonic and neonatal mammals.(6,7) The ability for an adult to develop new nephrons in response to toxic Injury appears to be unique to fish.

Developing nephrons have been demonstrated in adult goldfish exposed to a sublethal dose of hexachloro butadiene.(8,9) This response may provide investigators with a non-mammalian model for studying adult and developing nephrons in the same animal. The presence of large numbers of developing nephrons in adult feral fish may also serve as a biomarker for nephrotoxic contaminants in the environment.

Although fish have the ability to produce new nephrons following high doses of gentamicin, it is important to avoid nephrotoxicity when treating diseased fish. A healthy fish may be able to survive the osmoregulatory stress caused by tubular necrosis, but it is doubtful whether sick fish would do so. Further studies are needed to determine the effects of repeated smaller doses of gentamicin on the fish kidney.

This work was funded by a University of Maryland Institutional Designated Research Initiative Fund.

References

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2.  Riviere, J.E., M.P. Carver, G.L. Coppoc, W.W. Carlton, G.C. Lantz, J. ShyModjeska. 1984. Pharmacokinetics and comparative nephrotoxicity if fixed dose versus fixed-interval reduction of gentamicin dosage in subtotal nephrectomized dogs. Toxicol. and Applied Pharmacol. 75: 496-509.

3.  Houghton, DIC., M. Harnett, M., M. Campbell-boswell, G. Porter, W. Bennet. 1976. A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. Arn. J. Pathology 82: 589-612.

4.  Stoskopf, M.K. 1988. Fish chemotherapeutics. Vet. Clinics of N. America 18: 331348.

5.  Setser, M.D. 1985. Pharmacokinetics of gentamicin in channel catfish (Ictalurus punctatus). Am. J. Vet. Res. 46: 2558-2561.

6.  Larsson L. 1975. The ultrastructure of the developing proximal tubule in the rat kidney. J. Ultrastructure Res. 51: 119-139.

7.  Neiss W.F., Klehn K.L. 1981. The postnatal development of the rat kidney, with special reference to the chemodifferentiation of the proximal tubule. Histochemistry 73: 251-268.

8.  Reimschuessel, R., R.O. Bennett, E.B. May and M.M. Lipsky, 1990. Renal tubular cell regeneration, cell proliferation and chronic nephrotoxicity in the goldfish (Carassius auratus) following exposure to a single sublethal dose of hexachloro butadiene. Diseases of Aquatic Organisms 8: 211-224.

9.  Reimschuessel, R., R.O. Bennett, E.B. May and M.M. Lipsky, 1990. Development of newly formed nephrons in the goldfish kidney following hexachloro butadiene-induced nephrotoxicity. Toxicol. Pathol. 18: 32-38.