Renate Reimschuessel, VMD, PhD; Donna Williams, BS; Michael M. Lipsky, PhD
Department of Pathology, University of Maryland School of Medicine,
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.
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