Inhibition of mitochondrial respiration and oxygen uptake in isolated rat renal tubular fragments by atractyloside

Toxicology Letters
D K Obatomi, P H Bach

Abstract

Atractyloside (ATR) is widely used as a specific inhibitor of mitochondrial adenine nucleotide translocase and it is also a potent nephrotoxin that selectively injures the proximal tubule in vivo. This regioselectivity has been attributed to the prominence of mitochondria in the proximal tubule cells, but there have been no investigations to confirm this. In order to better understand the molecular basis of ATR-induced renal injury, oxidative phosphorylation was studied in freshly isolated rat proximal tubular and glomeruli fragments, and in isolated rat renal cortical mitochondria. In isolated renal mitochondrial, ATR significantly inhibited state 3 respiration in a dose-dependent manner, with the maximum inhibition achieved at the highest ATR concentration. Low doses of ATR (53 microM) inhibited respiration by 50%, an effect which was reversed by 2.5 mumol ADP. 2,4-Dinitrophenol (5 mM), which stimulated respiration in control mitochondria, failed to do this in the presence of ATR. Basal oxygen consumption was significantly inhibited by ATR (> 50 microM) in proximal tubule previously incubated for 1 h at 37 degrees C. The concentration-dependent inhibition of oxygen uptake by the proximal tubule was maintained in the presence ...Continue Reading

References

Apr 24, 1989·FEBS Letters·H Rottenberg, M Marbach
Jan 1, 1988·Journal of Toxicology. Clinical Toxicology·M GeorgiouA Koutselinis
Jul 1, 1987·Toxicology and Applied Pharmacology·G M KislingJ P Tow
Jan 1, 1974·Archives of Toxicology·F CarpenedoR Santi

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Citations

Aug 29, 2001·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D K ObatomiP H Bach
Jul 3, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D K Obatomi, P H Bach
Nov 28, 2008·Molecular Nutrition & Food Research·Michael V BerridgeAlfons Lawen
Jan 24, 2003·Human & Experimental Toxicology·M J StewartN J Crowther
Dec 29, 2000·Therapeutic Drug Monitoring·M J Stewart, V Steenkamp
Dec 8, 2016·Biological Chemistry·Rabia RamzanSebastian Vogt
Jun 27, 2019·Renal Failure·Nadezda PetejovaVladimir Teplan

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