Abstract

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.

Introduction

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.

Methods

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.

Results

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.

Discussion

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.

Acknowledgments

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 RR03061-11 l.

References

1.  Spangler WL, Adelman RD, Conzelman Jr. GM, Ishizaki G: Gentamicin nephrotoxicity in the Dog: Sequential light and electron microscopy. Vet Pathol 17:206­217, 1980.

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.