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L-carnitine as a means of preventing ototoxicity during gentamicin treatment

Gentamicin is a relatively inexpensive and often used antibacterial drug, but its use limits its inherent ototoxicity. However, in some cases, it remains the only therapeutic alternative, especially for the treatment of severe patients.

In a study by G.M. Kalinec et al. (USA), we investigated the mechanisms underlying hearing loss and loss during gentamicin therapy, as well as determining the effectiveness of L-carnitine in preventing the development of this adverse drug reaction. The basis of the work was data on the beneficial effect of this trace element on hearing in newborns suffering from neurological disorders.

The researchers observed pregnant guinea pigs receiving gentamicin at a dose of 100 mg / kg / day for 7 days. Treatment with L-carnitine started 2 weeks before or at the same time as the prescription of antibiotics. Using the methodology to determine the auditory evoked potentials of the brainstem, the researchers found that the hearing threshold for puppies not treated with gentamicin was 21 dB, while for puppies treated with the drug, it reached 30 dB. Administration of L-carnitine before or simultaneously with gentamicin led to changes in the hearing threshold level of 23 and 21 dB, respectively.

The results of confocal and electron microscopy indicated the beneficial effect of L-carnitine on external hair cells damaged by gentamicin. In a culture of hearing cells very sensitive to ototoxic drugs, it has been shown that gentamicin-induced ototoxicity is achieved by cell apoptosis which occurs when the proapoptotic gene Harakiri ( Hrk), which is mediated by extracellular, is activated signal regulated kinase (signal regulated extracellular kinase, ERK) and protein kinase activated by a mitogen (protein kinase activated by a mitogen, MAPK), as well as inhibition of the enzyme of the family of activated mitogen kinases JNK (c-Jun kinase N-terminal). L-carnitine is capable of preventing the inhibition of JNK and, consequently, the activation of the gene Hrk, thus blocking apoptosis of the hearing cells.

According to the authors, the results can be used as a basis for conducting clinical studies on the effectiveness of the use of L-carnitine in the prevention of gentamicin-induced ototoxicity.

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