Related Experiment Videos
Comparative nephrotoxicity of four aminoglycosides: biochemical and ultrastructural modifications of lysosomes
Abstract:
In 1982, aminoglycosides still are widely prescribed and considered indispensable for the treatment of severe gram-negative infections. All the aminoglycosides are nephrotoxic, but both experimental works and clinical investigations indicate that they do not all have the same nephrotoxic potential. Within the renal tubular cell in several animal species and in man, the initial and the most extensive changes are those that occur in the lysosomes. We compared the effects of gentamicin, tobramycin, netilmicin and, amikacin on (a) lysosomal structural latency, (b) the activity of several enzymes, either lysosomal or those contained in the proximal tubular cell brush border, and (c) the accumulation of myeloid bodies in the lysosomes. From our results, it appears that gentamicin is the aminoglycoside that induces the greatest number of lysosomal changes whereas amikacin induces the least, with the effects of netilmicin and tobramycin quite close to those of amikacin. Other works comparing the nephrotoxicity of aminoglycosides reveal the same high nephrotoxic potential of gentamicin.
Insights
Gentamicin and tobramycin show higher nephrotoxicity than amikacin and netilmicin in severe gram-negative infections. This study compares aminoglycoside effects on kidney cells, finding gentamicin causes the most lysosomal damage.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Aminoglycosides are crucial for treating severe gram-negative infections.
- All aminoglycosides exhibit nephrotoxicity, but their potential varies.
- Lysosomal changes are the earliest and most significant in renal tubular cells.
Purpose of the Study:
- To compare the nephrotoxic potential of four aminoglycosides: gentamicin, tobramycin, netilmicin, and amikacin.
- To evaluate their effects on lysosomal structural latency, enzyme activity, and myeloid body accumulation within renal tubular cells.
Main Methods:
- Experimental comparison of gentamicin, tobramycin, netilmicin, and amikacin.
- Assessment of lysosomal structural latency.
- Measurement of lysosomal and brush border enzyme activities.
- Quantification of myeloid body accumulation in lysosomes.
Main Results:
- Gentamicin induced the most significant lysosomal changes.
- Amikacin demonstrated the least nephrotoxic effects.
- Netilmicin and tobramycin exhibited effects closer to amikacin, indicating lower nephrotoxicity compared to gentamicin.
Conclusions:
- Aminoglycoside nephrotoxicity varies, with gentamicin posing the highest risk.
- Amikacin appears to be a safer alternative regarding kidney damage.
- Understanding these differences is vital for optimizing treatment strategies for severe gram-negative infections.