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Inhibition of mammalian microsomal protein synthesis by aminoglycoside antibiotics
Abstract:
The aminoglycoside antibiotics gentamicin, kanamycin and netilmicin produce a dose-dependent inhibition of amino acid incorporation in microsomes isolated from human liver and rat brain, kidney and liver. Inhibitory effects on microsomal protein synthesis occur at concentrations that have been shown to accumulate in rodent and human renal cortex and perilymph following therapeutic administration. Inhibition of translation in those tissues which specifically accumulate aminoglycoside antibiotics may, in part, explain toxicities observed following exposure to aminoglycosides.
Insights
Aminoglycoside antibiotics like gentamicin inhibit protein synthesis in the liver and brain. This inhibition, occurring at therapeutic concentrations, may explain observed toxicities in organs like the kidney.
Area of Science:
- Pharmacology and Toxicology
- Molecular Biology
- Biochemistry
Background:
- Aminoglycoside antibiotics are widely used for bacterial infections.
- These drugs are known to cause nephrotoxicity and ototoxicity.
- The precise molecular mechanisms underlying aminoglycoside toxicity are not fully understood.
Purpose of the Study:
- To investigate the effects of aminoglycoside antibiotics on protein synthesis.
- To determine if these effects occur at clinically relevant concentrations.
- To explore the potential link between protein synthesis inhibition and aminoglycoside-induced toxicity.
Main Methods:
- Isolated microsomes from human liver and rat brain, kidney, and liver tissues were used.
- Amino acid incorporation into proteins was measured to assess protein synthesis.
- Dose-dependent effects of gentamicin, kanamycin, and netilmicin were evaluated.
Main Results:
- Gentamicin, kanamycin, and netilmicin demonstrated a dose-dependent inhibition of amino acid incorporation.
- Inhibitory effects on microsomal protein synthesis were observed at concentrations found in renal cortex and perilymph.
- These concentrations are consistent with those achieved during therapeutic administration in rodents and humans.
Conclusions:
- Aminoglycoside antibiotics inhibit protein synthesis in a dose-dependent manner.
- Inhibition of translation in tissues that accumulate aminoglycosides may contribute to observed toxicities.
- This study provides a potential molecular explanation for aminoglycoside-induced organ damage.