Journal article

Methionine Ameliorates Polymyxin-Induced Nephrotoxicity by Attenuating Cellular Oxidative Stress

Mohammad AK Azad, Sivashangarie Sivanesan, Jiping Wang, Ke Chen, Roger L Nation, Philip E Thompson, Kade D Roberts, Tony Velkov, Jian Li

Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2018

Abstract

Polymyxins are a last line of defense against multidrug-resistant Gram-negative pathogens. Recent pharmacological data show that intravenous polymyxins can cause nephrotoxicity in up to 60% of patients, and the plasma concentrations of polymyxins achieved with the currently recommended dosage regimens are suboptimal in a large proportion of patients. Simply increasing the daily dose of polymyxins is not possible due to nephrotoxicity. This study aimed to examine the protective effect of methionine against polymyxin-induced nephrotoxicity. Methionine (400 mg/kg of body weight), polymyxin B (35 mg/kg), a combination of methionine (100 or 400 mg/kg) and polymyxin B, and saline were administered..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

This study is supported by a grant (APP1085637) from the Australian National Health and Medical Research Council (NHMRC). J.L. and T.V. are also supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI111965).