Ochratoxin A disturbs pH homeostasis in the kidney: increases in pH and HCO3- in the tubules and vasa recta.
This study was designed to elucidate the effects of ochratoxin A (OTA) on pH homeostasis in the kidney. We measured pH in the proximal (PT) and the distal (DT) tubular fluid, the collecting duct urine (CD), the descending and the ascending vasa recta blood (VR), and the renal arterial blood (RA). OTA increased pH significantly in PT, DT, CD as well as in the descending and ascending VR, whereas pH in RA remained unchanged. We further determined CO2 tension (pCO2) and HCO3- in PT, CD as well as in the descending and ascending VR. OTA significantly increased HCO3- in PT, CD and the descending and ascending VR, with no changes in pCO2. Therefore, the increases in pH in PT, CD and the descending and ascending VR result from the increase in HCO3-. Our results suggest that OTA inhibits HCO3- reabsorption in the tubules, leading to the impairment of urinary acidification, and that OTA further leads to the disturbance of the acid-base state (alkalinization) in the interstitium in renal papilla. The impairment of urinary acidification may contribute to the disturbance of pH homeostasis in the renal papilla. The disturbance of pH homeostasis by OTA could be related to its nephrotoxicity.
Kuramochi
G
G
Department of Physiology, University of Würzburg, Röntgenring 9, D-97070 Würzburg, Germany.
Gekle
M
M
Silbernagl
S
S
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D009183:Mycotoxins / Q000494:pharmacology*; D009793:Ochratoxins / Q000494:pharmacology*; D010313:Partial Pressure; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation
D001639:Bicarbonates; D009183:Mycotoxins; D009793:Ochratoxins; D002245:Carbon Dioxide; C025589:ochratoxin A; D006859:Hydrogen