Mechanisms of Polymyxin-Induced Nephrotoxicity.
Adv Exp Med Biol
; 1145: 305-319, 2019.
Article
en En
| MEDLINE
| ID: mdl-31364084
ABSTRACT
Polymyxin-induced nephrotoxicity is the major dose-limiting factor and can occur in up to 60% of patients after intravenous administration. This chapter reviews the latest literature on the mechanisms of polymyxin-induced nephrotoxicity and its amelioration. After filtration by glomeruli, polymyxins substantially accumulate in renal proximal tubules via receptor-mediated endocytosis mainly by megalin and PEPT2. It is believed that subsequently, a cascade of interconnected events occur, including the activation of death receptor and mitochondrial apoptotic pathways, mitochondrial damage, endoplasmic reticulum stress, oxidative stress and cell cycle arrest. The current literature shows that oxidative stress plays a key role in polymyxin-induced kidney damage. Use of antioxidants have a potential in the attenuation of polymyxin-induced nephrotoxicity, thereby widening the therapeutic window. Mechanistic findings on polymyxin-induced nephrotoxicity are critical for the optimization of their use in the clinic and the discovery of safer polymyxin-like antibiotics.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimixinas
/
Riñón
/
Enfermedades Renales
/
Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Australia