Ototoxicity of tobramycin sulfate

Prazma, Jiri; Postma, Duncan S.; Pecorak, John B.; Fischer, Newton D.

doi:10.1288/00005537-197602000-00022

Cited by 12 publications

(2 citation statements)

References 8 publications

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“…Over 90 % of type I afferents innervate IHCs with the remainder (∼10 %) innervating OHCs (Spoendlin 1975). Cochlear damage as a function of noise, ototoxic drugs, or ageing is associated with stereocilia dysfunction in IHCs and OHCs, damage to afferent fibers or synapses, and in many cases partial to complete loss of OHCs (Coleman 1976;McGill and Schuknecht 1976;Prazma et al 1976;Ryan et al 1980;Liberman and Dodds 1984;Soucek and Mason 1987). Hearing impairment associated with evidence of OHC damage or loss is generally characterized by increased thresholds and decreased frequency tuning (McGill and Schuknecht 1976;Dallos and Harris 1978;Stebbins et al 1979;Patuzzi et al 1989;Ohlms et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Lobariñas

Salvi

Ding

2015

JARO

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Poorer hearing in the presence of background noise is a significant problem for the hearing impaired. Ototoxic drugs, ageing, and noise exposure can damage the sensory hair cells of the inner ear that are essential for normal hearing sensitivity. The relationship between outer hair cell (OHC) loss and progressively poorer hearing sensitivity in quiet or in competing background noise is supported by a number of human and animal studies. In contrast, the effect of moderate inner hair cell (IHC) loss or dysfunction shows almost no impact on behavioral measures of hearing sensitivity in quiet, when OHCs remain intact, but the relationship between selective IHC loss and hearing in noise remains relatively unknown. Here, a moderately high dose of carboplatin (75 mg/kg) that produced IHC loss in chinchillas ranging from 40 to 80 % had little effect on thresholds in quiet. However, when tested in the presence of competing broadband (BBN) or narrowband noise (NBN), thresholds increased significantly. IHC loss 960 % increased signal-to-noise ratios (SNRs) for tones (500-11,300 Hz) in competing BBN by 5-10 dB and broadened the masking function under NBN. These data suggest that IHC loss or dysfunction may play a significant role in listening in noise independent of OHC integrity and that these deficits may be present even when thresholds in quiet are within normal limits.

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Section: Introductionmentioning

confidence: 99%

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Lobariñas

Salvi

Ding

2015

JARO

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“…The selected doses of the antibiotics were such that they were expected to induce gut dysbiosis. The high doses were selected to be as high as possible without inducing systemic toxicity and the low doses were 10 times lower than the high doses. − The high dose was never above 1000 mg/kg bw as this is the limit dose for oral administration according to OECD guidelines. Because there were no indications in the literature of toxicity, tobramycin was prepared in deionized water for oral administration at doses of 100 mg/kg body weight/day and 1000 mg/kg body weight/day, respectively.…”

Section: Methodsmentioning

confidence: 99%

Connecting Gut Microbial Diversity with Plasma Metabolome and Fecal Bile Acid Changes Induced by the Antibiotics Tobramycin and Colistin Sulfate

Murali

Giri

Zickgraf

et al. 2023

Chem. Res. Toxicol.

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The diversity of microbial species in the gut has a strong influence on health and development of the host. Further, there are indications that the variation in expression of gut bacterial metabolic enzymes is less diverse than the taxonomic profile, underlying the importance of microbiome functionality, particularly from a toxicological perspective. To address these relationships, the gut bacterial composition of Wistar rats was altered by a 28 day oral treatment with the antibiotics tobramycin or colistin sulfate. On the basis of 16S marker gene sequencing data, tobramycin was found to cause a strong reduction in the diversity and relative abundance of the microbiome, whereas colistin sulfate had only a marginal impact. Associated plasma and fecal metabolomes were characterized by targeted mass spectrometry-based profiling. The fecal metabolome of tobramycin-treated animals had a high number of significant alterations in metabolite levels compared to controls, particularly in amino acids, lipids, bile acids (BAs), carbohydrates, and energy metabolites. The accumulation of primary BAs and significant reduction of secondary BAs in the feces indicated that the microbial alterations induced by tobramycin inhibit bacterial deconjugation reactions. The plasma metabolome showed less, but still many alterations in the same metabolite groups, including reductions in indole derivatives and hippuric acid, and furthermore, despite marginal effects of colistin sulfate treatment, there were nonetheless systemic alterations also in BAs. Aside from these treatment-based differences, we also uncovered interindividual differences particularly centering on the loss of Verrucomicrobiaceae in the microbiome, but with no apparent associated metabolite alterations. Finally, by comparing the data set from this study with metabolome alterations in the MetaMapTox database, key metabolite alterations were identified as plasma biomarkers indicative of altered gut microbiomes resulting from a wide activity spectrum of antibiotics.

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