The aminoglycoside antibiotic gentamicin is able to alter metabolic activity and morphology of MDCK-C11 cells: a cell model of intercalated cells

Coutinho, Anna Gabrielle Gomes; Biscaia, Stellee Marcela Petris; Fernández, Ricardo; Tararthuch, A.L.

doi:10.1590/1414-431x20187417

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Approximately 25% of people who were administered with gentamicin have reported renal complications. This detrimental effect has been linked to the development of several alterations in the proximal tubule epithelium, followed by its annihilation, resulting in kidney failure (Coutinho et al, 2018; Randjelovic et al, 2017). Various gentamycin‐mediated detrimental effects due to intrinsic and extrinsic factors in renal cells can result in apoptosis and necrosis (Liu, 2019).…”

Section: Introductionmentioning

confidence: 99%

Retracted: Deacetyl epoxyazadiradione protects aminoglycoside antibiotic‐induced renal cell apoptosis, in vitro

Murugan

Rajesh

Velayutham

et al. 2022

Cell Biology International

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Aminoglycoside antibiotics such as gentamicin are used frequently to treat bacterial infections in humans. Excessive consumption of these antibiotics lead to renal dysfunction. One of the factors contributing to renal dysfunction is oxidative damage, which causes apoptosis. Hence, this study investigates the effect of the antioxidant compound deacetyl epoxyazadiradione (DEA) in reducing cell death induced by gentamicin treatment in kidney cells (Madin-Darby canine kidney cells).The antioxidant experiments showed that reactive oxygen species level is decreased up to 27.06 ± 0.18% in 150 µM of DEA treatment. At this concentration, the activity of antioxidant enzymes such as superoxide dismutase increased from 0.4 ± 0.04 to 1.46 ± 0.05 µmol/min/L and catalase increased from 7.48 ± 0.39 to 17.6 ± 0.74 U/ mg. The relative folds of gene expression of mitochondrial enzymes such as GST, GPx and GR restored from 0.596 ± 0.019, 0.521 ± 0.013 and 0.775 ± 0.014 to 0.866 ± 0.013, 0.669 ± 0.015 and 0.8615 ± 0.028, respectively. Consequently, the percentage of cell viability increases upto 91.8 ± 2.01 from 61.93 ± 1.63 with much less fragmentation in genomic DNA. Additionally, molecular docking results showed that DEA could bind to Bax, Bcl-2, Caspase-3 and Caspase-9 proteins. These results indicate that DEA could reduce cell apoptosis by reducing oxidative stress due to antibiotics and interrupting the apoptotic signal pathway in kidney cells.

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Section: Introductionmentioning

confidence: 99%

Retracted: Deacetyl epoxyazadiradione protects aminoglycoside antibiotic‐induced renal cell apoptosis, in vitro

Murugan

Rajesh

Velayutham

et al. 2022

Cell Biology International

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“…However, its use is restricted because of the development of nephrotoxicity 12 . Nephrotoxicity has been related to a selective accumulation of gentamicin in the renal cortex 13 . GM causes renal morphological changes and an overall syndrome very similar in humans and experimental animals 14 .…”

Section: Introductionmentioning

confidence: 99%

Phytochemical analysis, antioxidant activity, and nephroprotective effect of the Raphanus sativus aqueous extract

et al. 2021

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In Morocco, Raphanus sativus is a widespread traditional medicinal plant used to treat various kidney diseases such as nephropathy.Objective: The present study aims to evaluate the protective effect of the R. sativus aqueous extract against the gentamicin-induced acute nephrotoxicity in rats.Methods: Rats were randomly separated into four groups (n=6; ♂/ ♀=1). The control group was treated only with distilled water (10 mL/kg; p.o). The gentamicin group was treated with distilled water (10 mL/kg; p.o) and injected intraperitoneally by the gentamicin (80 mg/kg; i.p). R. sativus groups were treated with the aqueous extracts of this plant at a dose of (200 or 400 mg/kg; p.o) and injected by the gentamicin (80 mg/kg; i.p). The plasma Creatinine, Urea, Uric Acid, Albumin, Total Protein, Alanine transaminase, Aspartate transaminase, and Calcium levels were measured. The urinary creatinine, urinary Calcium, urinary volume, water intake, creatinine clearance, body weight gain, relative right kidney weight, and kidney malondialdehydes were determined.Results: This study showed that the daily pretreatment with R. sativus aqueous extract at two doses of 200 and 400 mg/kg, p.o prevented the rats from the gentamicin-induced nephrotoxicity. Moreover, the R. sativus aqueous extract showed a high amount of polyphenols and flavonoids and a significant antioxidant activity.Conclusion: R. sativus aqueous extract, as a novel natural product, may have preventive properties against gentamicin-induced nephrotoxicity in rats. The present study describes new areas of investigation to introduce better therapeutic agents for renal disorders and dysfunction.

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“…Gentamicin is an antibiotic drug from the aminoglycoside class, produced by fermentation by Micromonospora purpurea, and was discovered in 1963 [1,2]. Gentamicin and other aminoglycosides are typically used in combination with a penicillin or cephalosporin for treatment of severe infections with E. coli, Staphylococcus aureus, Enterobacter, Klebsiella, Pseudomonas aeruginosa, and other gramnegative bacteria resistant to less toxic antibiotics [3,4].…”

Section: Introductionmentioning

confidence: 99%

Saliva versus Plasma Therapeutic Drug Monitoring of Gentamicin in Jordanian Preterm Infants. Development of a Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class II Drugs of Salivary Excretion Classification System

et al. 2020

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Gentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5–7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients.

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The aminoglycoside antibiotic gentamicin is able to alter metabolic activity and morphology of MDCK-C11 cells: a cell model of intercalated cells

Cited by 6 publications

References 24 publications

Retracted: Deacetyl epoxyazadiradione protects aminoglycoside antibiotic‐induced renal cell apoptosis, in vitro

Retracted: Deacetyl epoxyazadiradione protects aminoglycoside antibiotic‐induced renal cell apoptosis, in vitro

Phytochemical analysis, antioxidant activity, and nephroprotective effect of the Raphanus sativus aqueous extract

Saliva versus Plasma Therapeutic Drug Monitoring of Gentamicin in Jordanian Preterm Infants. Development of a Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class II Drugs of Salivary Excretion Classification System

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