Abstract
It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.
Highlights
Gentamicin is an aminoglycoside antibiotic that has a broad spectrum of action against gram-negative bacterial infections and it is more recommended in severe cases [1]
Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin in proximal tubules, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity, using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron
When the cells were incubated with 0.3 mM Gd3+, a calciumsensing receptor (CaSR) agonist, the cytosolic ionized calcium increased to 107.9±19.6% after 10 min, 111.9± 9.3% after 20 min, and 116.1±8.0% after 30 min
Summary
Gentamicin is an aminoglycoside antibiotic that has a broad spectrum of action against gram-negative bacterial infections and it is more recommended in severe cases [1]. Since their development in 1940, aminoglycosides are preferably used in antimicrobial therapy. Gentamicin remains popular because it is a low-cost, quite effective antibiotic, demonstrating low antimicrobial resistance [2]. Many studies were designed to reveal the underlying mechanism of its ototoxic and nephrotoxic effects. Gentamicin-induced nephrotoxicity occurs in about 10 to 20% of treatments, and the progression to acute renal failure typically manifests after 5–7 days of treatment [3]. In patients treated for more than 14 days, nephrotoxicity appears in about 50% of them, resulting in increased morbidity during and after treatment [4]
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