Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats

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Published inAntimicrobial Agents and Chemotherapy Vol. 55; no. 9; pp. 4044 - 4049
Main Authors Yousef, Jumana M, Chen, Gong, Hill, Prue A, Nation, Roger L, Li, Jian
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.09.2011
Subjects
Acetylglucosaminidase - urine
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Colistin
Colistin - toxicity
Creatinine - blood
Experimental Therapeutics
Kidney
Kidney - drug effects
Male
Medical sciences
Melatonin
Melatonin - therapeutic use
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Melatonin
Urinary system disease
Colistin
Rat
Cyclic peptides
Toxicity
Rodentia
Kidney
Vertebrata
Antibiotic
Mammalia
Polypeptide
Animal
Antibacterial agent
Pineal hormone
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Colistin-induced nephrotoxicity is a dose-limiting adverse effect when colistin is used against Gram-negative pathogens. This study examined the nephroprotective effect of melatonin against colistin in rats. Rats (n = 7 per group) were treated intravenously twice daily with saline, colistin (at increasing doses from 0.5 to 4.0 mg/kg), melatonin (5 mg/kg), or both melatonin and colistin for 7 days. The severity of renal alteration was examined both biochemically and histologically. The effect of coadministration of melatonin on colistin pharmacokinetics was investigated. Significantly lower urinary N-acetyl-β-d-glucosaminidase excretion was observed from day 1 in the colistin-melatonin group compared to the colistin group (P < 0.0001). Plasma creatinine increased significantly (P = 0.023) only in the colistin group on day 6. Significant histological abnormalities (P < 0.0001) were detected only in the kidneys of the colistin group. Melatonin altered colistin pharmacokinetics; the total body clearance in the colistin-melatonin group (1.82 ± 0.26 ml/min/kg) was lower than in the colistin group (4.28 ± 0.93 ml/min/kg). This is the first study demonstrating the protective effect of melatonin against colistin-induced nephrotoxicity, which indicates that colistin-induced nephrotoxicity is mediated through oxidative stress. It also highlights the potential of coadministering an antioxidant to widen the therapeutic window of this very important last-line antibiotic.
Colistin-induced nephrotoxicity is a dose-limiting adverse effect when colistin is used against Gram-negative pathogens. This study examined the nephroprotective effect of melatonin against colistin in rats. Rats ( n = 7 per group) were treated intravenously twice daily with saline, colistin (at increasing doses from 0.5 to 4.0 mg/kg), melatonin (5 mg/kg), or both melatonin and colistin for 7 days. The severity of renal alteration was examined both biochemically and histologically. The effect of coadministration of melatonin on colistin pharmacokinetics was investigated. Significantly lower urinary N -acetyl-β- d -glucosaminidase excretion was observed from day 1 in the colistin-melatonin group compared to the colistin group ( P < 0.0001). Plasma creatinine increased significantly ( P = 0.023) only in the colistin group on day 6. Significant histological abnormalities ( P < 0.0001) were detected only in the kidneys of the colistin group. Melatonin altered colistin pharmacokinetics; the total body clearance in the colistin-melatonin group (1.82 ± 0.26 ml/min/kg) was lower than in the colistin group (4.28 ± 0.93 ml/min/kg). This is the first study demonstrating the protective effect of melatonin against colistin-induced nephrotoxicity, which indicates that colistin-induced nephrotoxicity is mediated through oxidative stress. It also highlights the potential of coadministering an antioxidant to widen the therapeutic window of this very important last-line antibiotic.
Author Jumana M. Yousef
Jian Li
Prue A. Hill
Gong Chen
Roger L. Nation
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Copyright © 2011, American Society for Microbiology. All Rights Reserved.
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Issue 9
Keywords Melatonin
Urinary system disease
Colistin
Rat
Cyclic peptides
Toxicity
Rodentia
Kidney
Vertebrata
Antibiotic
Mammalia
Polypeptide
Animal
Antibacterial agent
Pineal hormone
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PublicationTitle Antimicrobial Agents and Chemotherapy
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e_1_3_2_26_2
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e_1_3_2_27_2
e_1_3_2_28_2
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e_1_3_2_41_2
Tomas-Zapico C. (e_1_3_2_48_2) 2007; 1
e_1_3_2_20_2
e_1_3_2_43_2
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Nation R. L. (e_1_3_2_34_2) 2010
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e_1_3_2_14_2
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Racusen L. (e_1_3_2_40_2) 2007
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  doi: 10.1007/s10096-006-0191-2
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Colistin-induced nephrotoxicity is a dose-limiting adverse effect when colistin is used against Gram-negative pathogens. This study examined the...
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SubjectTerms Acetylglucosaminidase - urine
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Colistin
Colistin - toxicity
Creatinine - blood
Experimental Therapeutics
Kidney
Kidney - drug effects
Male
Medical sciences
Melatonin
Melatonin - therapeutic use
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Title Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats
URI http://aac.asm.org/content/55/9/4044.abstract
https://www.ncbi.nlm.nih.gov/pubmed/21709095
https://journals.asm.org/doi/10.1128/AAC.00328-11
https://pubmed.ncbi.nlm.nih.gov/PMC3165279
Volume 55
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