A systematic review and meta-analysis of the efficacy and safety of<i>N</i>-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB

Kranzer, Katharina; Elamin, Wael; Cox, Helen; Seddon, James A; Ford, Nathan; Drobniewski, Francis

doi:10.1136/thoraxjnl-2015-207245

Cited by 58 publications

(43 citation statements)

References 64 publications

(32 reference statements)

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“…C‐terminally extended aberrant proteins produced as a result of gentamycin treatment are presented by MHC class I molecules, which may invoke autoimmune diseases . Therefore, understanding the quality control mechanism regulating 3′‐UTR translation would contribute to alleviating the side effects of aminoglycosides including ototoxicity and renal failure . Ataluren, formerly known as PTC124, is used for the treatment of Duchenne muscular dystrophy (DMD) .…”

Section: Resultsmentioning

confidence: 99%

“…The correlation coefficients (R) between the MKD and the RFP/GFP ratio of mutants are shown on the bottom right of the bar graph of the RFP/GFP ratio. regulating 3 0 -UTR translation would contribute to alleviating the side effects of aminoglycosides including ototoxicity and renal failure [48]. Ataluren, formerly known as PTC124, is used for the treatment of Duchenne muscular dystrophy (DMD) [49][50][51][52].…”

Section: Translation Arrest At the 3 0 -Utr Contributes To Downregulamentioning

confidence: 99%

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Translation arrest as a protein quality control system for aberrant translation of the 3′‐UTR in mammalian cells

et al. 2019

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Read‐through or mutations of a stop codon resulting in translation of the 3′‐UTR produce potentially toxic C‐terminally extended proteins. However, quality control mechanisms for such proteins are poorly understood in mammalian cells. Here, a comprehensive analysis of the 3′‐UTRs of genes associated with hereditary diseases identified novel arrest‐inducing sequences in the 3′‐UTRs of 23 genes that can repress the levels of their protein products. In silico analysis revealed that the hydrophobicity of the polypeptides encoded in the 3′‐UTRs is correlated with arrest efficiency. These results provide new insight into quality control mechanisms mediated by 3′‐UTRs to prevent the production of C‐terminally extended cytotoxic proteins.

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Section: Resultsmentioning

confidence: 99%

Section: Translation Arrest At the 3 0 -Utr Contributes To Downregulamentioning

confidence: 99%

Translation arrest as a protein quality control system for aberrant translation of the 3′‐UTR in mammalian cells

et al. 2019

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“…In previous clinical studies, some side effects were observed after NAC treatment against aminoglycosideinduced ototoxicity for more than 6 weeks, such as abdominal pain, nausea, vomiting and diarrhea. [22][23][24] In the future studies, the toxic effects of NAC after longterm treatment should be further evaluated.…”

Section: Discussionmentioning

confidence: 99%

N‐Acetylcysteine alleviates gut dysbiosis and glucose metabolic disorder in high‐fat diet‐fed mice

Zheng

Yuan

Zhang

et al. 2018

Journal of Diabetes

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“…However, the efficacy of this dose is unclear, and the use of this dose is not currently recommended. Other possibilities include the coadministration of N-acetylcysteine or other antioxidants (23), genetic testing for mutations in the mitochondrial gene encoding 12S rRNA (MT-RNR1), and avoiding aminoglycosides in patients with these mutations (24)(25)(26), though the prevalence of these mutations is low.…”

Section: Discussionmentioning

confidence: 99%

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

Arnold

Cooke

Kon

et al. 2017

Antimicrob Agents Chemother

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The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n ϭ 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n ϭ 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n ϭ 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P ϭ 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fiftyfive percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P ϭ 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of Ͼ1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.

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A systematic review and meta-analysis of the efficacy and safety ofN-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB

Cited by 58 publications

References 64 publications

Translation arrest as a protein quality control system for aberrant translation of the 3′‐UTR in mammalian cells

Translation arrest as a protein quality control system for aberrant translation of the 3′‐UTR in mammalian cells

N‐Acetylcysteine alleviates gut dysbiosis and glucose metabolic disorder in high‐fat diet‐fed mice

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

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