The synthetic polyphenol tert-butyl-bisphenol inhibits myoglobin-induced dysfunction in cultured kidney epithelial cells

Abstract

Rhabdomyolysis caused by severe burn releases extracellular myoglobin (Mb) that accumulates in the kidney and urine (maximum [Mb] ∼ 50 μM) (termed myoglobinuria). Extracellular Mb can be a pro-oxidant. This study cultured Madin-Darby-canine-kidney-Type-II (MDCK II) cells in the presence of Mb and tested whether supplementation with a synthetic tert-butyl-polyphenol (tert-butyl-bisphenol; t-BP) protects these renal cells from dysfunction. In the absence of t-BP, cells exposed to 0–100 μM Mb for 24 h showed a dose-dependent decrease in ATP and the total thiol (TSH) redox status without loss of viability. Gene expression of superoxide dismutases-1/2, haemoxygenase-1 and tumour necrosis factor increased and receptor-mediated endocytosis of transferrin and monolayer permeability decreased significantly. Supplementation with t-BP before Mb-insult maintained ATP and the TSH redox status, diminished antioxidant/pro-inflammatory gene responses, enhanced monolayer permissiveness and restored transferrin uptake. Overall, bolstering the total antioxidant capacity of the kidney may protect against oxidative stress induced by experimental myoglobinuria.

Keywords::

• Antioxidant
• oxidative stress
• myoglobinuria
• burns
• polyphenol
• acute renal failure

Declaration of interest: We thank the support from the Australian Research Council (Fellowship DP0343325 and Discovery DP0878559 Grants to PKW). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 20 May 2010.