(-)-α-Bisabolol as a protective agent against epithelial renal cytotoxicity induced by amphotericin B

Introduction: Amphotericin B (AmB), used for systemic fungal infections, has a limited clinical application because of its high nephrotoxicity. Natural antioxidant and anti-inflammatory substances have been widely studied for protection against drug-induced nephrotoxicity. alpha-Bisabolol (BIS) has demonstrated a nephroprotective effect on both in vitro and in vivo models. Aims: The aim of this work was to evaluate the effect of BIS against AmB-induced nephrotoxicity in vitro.Material and methods: LLC-MK2 cells were pre-and post-treated with non-toxic BIS concentrations and/or AmB IC50 (13.97 mu M). Cell viability was assessed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Flow cytometry analyses were used to assess cell death mechanism, production of reactive oxidative stress (ROS) and mitochondrial transmembrane potential. Kidney Injury Molecule-1 (KIM-1) levels were measured via ELISA. Key findings: The present work showed that BIS pretreatment (125; 62.5 and 31.25 mu M) increased cell viability when compared to the group treated only with AmB IC50. AmB treatment induced both necrosis (7-AAD-labeled cells) and late apoptosis (AnxV-labeled). BIS was able to prevent the occurrence of these events. These effects were associated with a decrease of ROS accumulation, improving transmembrane mitochondrial potential and protecting against tubular cell damage, highlighted by the inhibition of KIM-1 release after BIS treatment.Significance: BIS presented a potential effect on model of renal cytotoxicity induced by AmB, bringing perspectives for the research of new nephroprotective agents.