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IMPACT OF GENTAMICIN ON ANTIOXIDANT ENZYMES ACTIVITY IN HEMn-DP CELLS
Abstract:
Aminoglycoside antibiotics, including gentamicin, are widely used clinically in treatment of bacterial infections. Unfortunately, their side effects, especially nephrotoxicity and ototoxicity remain a problem. It is known that aminoglycoside antibiotics bind well to melanin biopolymer, but the relation between their affinity to melanin and ototoxicity is not well documented. The aim of this work was to examine the impact of gentamicin on antioxidant enzymes activity in cultured dark pigmented normal human melanocytes (HEMn-DP). The WST-1 assay was used to detect gentamicin cytotoxic effect. The analyzed antibiotic induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be 7.5 mM. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to gentamicin, what may indicate the depletion of antioxidant defense system. It is concluded, that the results obtained in vitro may explain a potential role of melanocytes and melanin in the causative mechanisms of aminoglycosides ototoxic effects in vivo.
Insights
Gentamicin, an antibiotic, harms antioxidant defenses in melanocytes, potentially explaining its ototoxicity. This study investigated gentamicin
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Aminoglycoside antibiotics like gentamicin are crucial for bacterial infections but cause nephrotoxicity and ototoxicity.
- The binding of aminoglycosides to melanin is known, yet its link to ototoxicity is unclear.
- Melanocytes, pigment-producing cells, are potential targets for aminoglycoside-induced damage.
Purpose of the Study:
- To investigate the effect of gentamicin on antioxidant enzyme activity in cultured human melanocytes (HEMn-DP).
- To explore the potential role of melanocytes and melanin in aminoglycoside-induced ototoxicity.
Main Methods:
- Cell viability was assessed using the WST-1 assay to determine gentamicin's cytotoxic effect.
- Activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was measured in melanocytes exposed to gentamicin.
Main Results:
- Gentamicin induced a concentration-dependent decrease in melanocyte viability, with an EC50 value of 7.5 mM.
- Significant alterations in SOD, CAT, and GPx activity were observed in melanocytes treated with gentamicin.
- These changes suggest a depletion of the antioxidant defense system within melanocytes.
Conclusions:
- In vitro results indicate that gentamicin negatively impacts antioxidant enzymes in melanocytes.
- Melanocytes and melanin may play a role in the mechanisms underlying gentamicin's ototoxicity.
- Further research is warranted to elucidate the in vivo implications of these findings.
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