S. Chamie; R. Reimschuessel, VMD, PhD
Aquatic Pathobiology Center, Department of Pathology, University of
Maryland School of Medicine, Baltimore, MD
The aminoglycoside antibiotic gentamicin has been used to treat
individual fish with gram negative bacterial infections. However, safe therapeutic doses
have only been published for several species. During a recent investigation using the oyster
toadfish (Opsanus tau) we have determined that even very low doses of gentamicin are
extremely nephrotoxic. Because of the variability in fish kidney anatomy between different
species, it is important to evaluate therapeutic agents in multiple species or families.
Aminoglycoside nephrotoxicity has been demonstrated in multiple
mammalian species (1,2) and also in fish (3). Detailed pharmacokinetic information for the
aminoglycoside gentamicin is generally unavailable for most fish species. The therapeutic
dose for the channel catfish has been calculated to be 3.5 mg/kg given at 33 hour intervals
(4). For the clinician faced with multiple species, it is tempting to utilize this dose for
other species of fish. There are, however, significant risks for generalizing what was found
in one species to other species. There many anatomic variations in different fish families
that could impact the toxicity of different drugs. We report here the effect of different
doses of gentamicin on the oyster toadfish kidney.
Oyster toadfish were collected locally and brought to the University
of Maryland Aquatic Pathobiology Center. Fish were maintained in a closed-recirculating
system at 15 ppt salinity. Fish were injected with 50, 15, 5 and 2.5 mg/kg gentamicin IP.
Animals were sacrificed at various time intervals after the injection, 3 days, 1 week and 2
weeks. Kidneys were removed, preserved in 10% phosphate buffered formalin and routine
H&E sections were examined by light microscopy.
The oyster toadfish kidney contains proximal tubules, collecting ducts
and hematopoetic interstitial cells. There are no glomeruli and no distal tubules in this
species. Extensive necrosis of the proximal tubules was found three days following injection
at every dose of gentamicin. Over the next two weeks there was a loss of normal tubular
architecture throughout the kidneys and a dilation of the collecting ducts. Little repair
along the nephron was noted in the 50, 15 and 5 mg/kg doses. Some regeneration along the
basement membrane was noted in the 2.5 mg/kg dose by 2 weeks. The fish appeared grossly
normal throughout the experiment but the high dose fish (50,15) refused to eat.
These experiments show that the oyster toadfish kidney is quite
sensitive to gentamicin induced nephrotoxicity. A single injection of 2.5 mg/kg induced
extensive necrosis and tubule loss which continued for several weeks. The therapeutic dose
for the channel catfish, found in many of the same waters, is 3.5 mg/kg repeated at 33 hour
intervals. Since a single injection caused such extensive damage, repeated doses would only
enhance the injury. The fish did not show any overt clinical signs of the toxicity. In a
clinical setting, one would probably not be aware of the iatrogenic damage induced by the
treatments. Any additional stressors on the fish, however, would probably cause the animal's
condition to deteriorate. It is important, when dealing with multiple species, to obtain as
much information about treatment regimes as possible. Unfortunately, clinicians are often
faced with the necessity to treat animals with drugs for which no data is available. It is
important then to obtain as much information as possible while using such drugs; observe the
animals, record feeding and other behavior and if the animals die, conduct gross and
histological examinations of the tissues.
The authors would like to acknowledge the kind help of Mr. R.
Lukacovic and Dr. Eric May of the Md. Dept. of Natural Resources for obtaining the fish.
This study was supported in part by NCRR, NIH Biomedical Research Support Program grant
1. Spangler WL, Adelman RD, Conzelman Jr. GM, Ishizaki G:
Gentamicin nephrotoxicity in the Dog: Sequential light and electron microscopy. Vet Pathol
2. Houghton DC, Harnett M, Campbell-boswell M, Porter G,
Bennet W: A light and electron microscopic analysis of gentamicin nephrotoxicity in rats.
Am. J. Pathology 82:589-612, 197.
3. Reimschuessel R, Williams D, Lipsky MM. Gentamicin toxicity
induces development of new nephrons in goldfish. Presented at the 22nd annual International
Assoc. for Aquatic Animal Medicine Conference, Orlando, Fl. May 1991.
4. Setser, MD: Pharmacokinetics of gentamicin in channel
catfish (Ictalurus punctatus). Am. J. Vet Res. 46: 2558-2561, 1985.