Effects of systemic versus local gentamicin on the inner ear in the Atlantic cod, Gadus morhua (L.), relevance for fish hearing investigations

Abstract

a b s t r a c tFish models are increasingly being used for hearing research investigations. Aminoglycoside antibiotics that are used for damaging the inner ear hair cells can have systemic side effects leading to death of study animals. This study aimed to compare two methods: (i) systemic (intravenous) and (ii) local (intrasaccular) gentamicin administration for induction of inner ear hair cell damage in the Atlantic cod, Gadus morhua (L.). Hair cell damage was assessed using scanning electron microscopy; hair cell density, prevalence of immature hair cells and kinocilia length were measured. Gentamicin-treated fish were compared with control and sham fish. Intravenous gentamicin led to dose-dependent mortality caused by nephrotoxicity. The only visible effect after treatment was more immature hair cells and shorter kinocilia, the effect on hair cell density was equivocal. Following intrasaccular gentamicin treatment, fish mortality was negligible, and hair cells were damaged regardless of dose. Here, we observed decreased hair cell density, high prevalence of immature hair cells, and significantly shortened kinocilia. Conclusion: intrasaccular injection is preferable to intravenous injection of gentamicin for the study of ototoxicity in the Atlantic cod.

Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin

“…Aminoglycoside antibiotics are commonly used for damage of sensory hair cells in the fish lateral line system (Kaus, 1987;Song et al, 1995;Harris et al, 2003;Santos et al, 2006) and inner ear (Matsuura et al, 1971;Yan et al, 1991;Lombarte et al, 1993). In the past, intramuscular (Yan et al, 1991;Lombarte et al, 1993) or intravenous (Faucher et al, 2008) gentamicin injections have been used to study sensory hair cell regeneration in fish. However, systemic administration of aminoglycosides may be accompanied by unwanted side-effects, like nephrotoxicity and subsequent mortality of study animals.…”

“…However, systemic administration of aminoglycosides may be accompanied by unwanted side-effects, like nephrotoxicity and subsequent mortality of study animals. Matsuura et al (1971) used intrasaccular kanamycin and streptomycin injections into the goldfish (Carassius auratus) inner ear, and our group has recently demonstrated that local injection of gentamicin directly into the inner ear sacculus is an efficient method to obtain inner ear damage without undue side effects in the Atlantic cod (Faucher et al, 2008). Until now, most studies showing effect of aminoglycoside antibiotics on fish inner ear hair cells have considered either the functional aspects (Matsuura et al, 1971) or the ultrastructural damage and recovery (Yan et al, 1991;Lombarte et al, 1993;Schö nleber & Anken, 2004) following an ototoxic intervention.…”

“…Injections were done in the same manner as described in a previous publication (Faucher et al, 2008). Intraluminal saccular injections of 0.05 ml of saline (sham fish) or gentamicin (treated fish) were performed in the anaesthetized fish fixed in a polystyrene gutter.…”

“…Correct positioning of the needle inside the inner ear sacculi was ascertained in every fish using X-ray imaging. The volume and dose of injected gentamicin corresponded to our previous study (Faucher et al, 2008).…”

“…In order to examine the effect of intrasaccular injection of saline or gentamicin on inner ear sensory hair cells, the ultrastructural status of the inner ear sacculi was compared between groups. SEM pictures of local population samples were taken at three different locations in the area close to the wide indentation in the ventral margin of the macula sacculi (Faucher et al, 2008). Micrographs at 1500) magnification were taken at each sample location to show an area of 5000 mm 2 .…”