Comparative Surface Studies of Ototoxic Effects of Various Aminoglycoside Antibiotics on the Organ of Corti in the Guinea Pig A Scanning Electron Microscopic Study

Theopold, Hans-Martin

doi:10.3109/00016487709123942

Cited by 47 publications

(14 citation statements)

References 6 publications

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“…Aminoglycosides are clinically used drugs that cause dose-dependent sensorineural hearing loss (Smith et al, 1977) and are known to kill hair cells in the mammalian inner ear (Theopold, 1977). The mechanisms of aminoglycoside-induced hair cell toxicity are an area of active investigation.…”

Section: Introductionmentioning

confidence: 99%

Lateral line hair cell maturation is a determinant of aminoglycoside susceptibility in zebrafish (Danio rerio)

Santos¹,

MacDonald²,

Rubel³

et al. 2006

Hearing Research

128

156

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Section: Introductionmentioning

confidence: 99%

Lateral line hair cell maturation is a determinant of aminoglycoside susceptibility in zebrafish (Danio rerio)

Santos¹,

MacDonald²,

Rubel³

et al. 2006

Hearing Research

128

156

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“…Gentamicin (GM), which is one of the most commonly used aminoglycoside antibiotics, can induce hearing loss and balance disturbance due to the destruction of cochlear and vestibular hair cells [7]. The exact mechanism of GM-induced ototoxicity is unclear.…”

Section: Introductionmentioning

confidence: 99%

Anti-apoptotic effect of dexamethasone in an ototoxicity model

Lee

Kim

et al. 2017

Biomater Res

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BackgroundDexamethasone (DEX) is used for the treatment of various inner ear diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell damage is not known. Therefore, this study investigated the protective effect of DEX on gentamicin (GM)-induced ototoxicity and the effect of GM on the expression of apoptosis related genes.MethodsThe protective effects of DEX were measured by phalloidin staining of explant cultures of organ of Corti from postnatal day 2–3 mice with GM-induced hair cell loss. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to detect apoptosis and immunofluorescence was done to analyze the effect of DEX on the expression of apoptosis related genes.ResultsCochlear explant cultures of postnatal day-4-old mice were exposed to 0, 1, 5, 10, 30, 50, and 100 μg/ml DEX and GM during culture. DEX protected from GM-induced hair cell loss in the inner ear of postnatal day 4 mice. To understand the molecular mechanisms by which DEX pre-treatment decreased hair cell loss, the testes of cochlear explant cultures of postnatal day 4 mice were examined for changes in expression of cochlear apoptosis mediators. The pro-apoptotic protein Bax was significantly down-regulated and numbers of apoptotic hair cells were decreased.ConclusionsDEX has a protective effect on GM-induced hair cell loss in neonatal cochlea cultures and the protective mechanism may involve inhibition of the mitochondrial apoptosis pathway. The combination with scaffold technique can improve delivery of DEX into the inner ear to protect GM-induced ototoxicity.

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“…It has been reported that the aminoglycoside antibiotics that are widely used in clinical practice, such as gentamicin, tobramycin, and amikacin, show similar perilymph drug concentrations (5) and provoke substantially overlapping ototoxic reactions (1,3,5,9). Studies on neomycin, streptomycin, dihydrostreptomycin, and kanamycin (8,11) also have shown that the relative ability of each aminoglycoside antibiotic to reach greater perilymph concentration was directly related to the extent of their ototoxic damage in guinea pigs.…”

mentioning

confidence: 99%

Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs

Chung¹,

Parravicini²,

Assael³

et al. 1982

Antimicrob Agents Chemother

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The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous Ototoxicity on both the vestibular and cochlear portions of the inner ear is a recognized side effect of aminoglycoside antibiotic therapy. It has been reported that the aminoglycoside antibiotics that are widely used in clinical practice, such as gentamicin, tobramycin, and amikacin, show similar perilymph drug concentrations (5) and provoke substantially overlapping ototoxic reactions (1, 3, 5, 9). Studies on neomycin, streptomycin, dihydrostreptomycin, and kanamycin (8, 11) also have shown that the relative ability of each aminoglycoside antibiotic to reach greater perilymph concentration was directly related to the extent of their ototoxic damage in guinea pigs. These data suggest a possible relationship between the drug concentration achieved in the inner ear and the ototoxicity of aminoglycoside antibiotics.Netilmicin, a new semisynthetic aminoglycoside antibiotic and a 1-N-ethyl derivative of sisomicin, has been demonstrated in animals to be several times less ototoxic (1, 2, 4, 12) than gentamicin, tobramycin, sisomicin, amikacin, and kanamycin. Since the available information on the pharmacokinetics of aminoglycoside antibiotics in guinea pigs is limited, the present study was conducted to obtain detailed pharmacokinetics of gentamicin, netilmicin, and tobramycin in the perilymph as well as in the plasma of guinea pigs. A possible relationship between the pharmacokinetic properties of the aminoglycoside antibiotics and their comparative ototoxicities was also examined. MATERIALS AND METHODSStudy procedure. A total of 157 guinea pigs weighing between 300 and 350 g and with normal Preyer's reflex were used in this study.For the pharmacokinetic study in plasma, 15 of the experimental animals were randomly divided into three drug treatment groups of 5 animals each. Each animal was anesthetized with tribromoethanol (200 mg/kg, intraperitoneal injection), and both the left jugular vein and right carotid artery were cannulated. The animals were then placed in restricted cages. After complete recovery from anesthesia, the assigned drug (gentamicin, netilmicin, or tobramycin) was administered intravenously into the jugular vein at a dose of 40

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Comparative Surface Studies of Ototoxic Effects of Various Aminoglycoside Antibiotics on the Organ of Corti in the Guinea Pig A Scanning Electron Microscopic Study

Cited by 47 publications

References 6 publications

Lateral line hair cell maturation is a determinant of aminoglycoside susceptibility in zebrafish (Danio rerio)

Lateral line hair cell maturation is a determinant of aminoglycoside susceptibility in zebrafish (Danio rerio)

Anti-apoptotic effect of dexamethasone in an ototoxicity model

Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs

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