The effects of potassium chromate and citrinin on rat renal membrane transport.
Both chromate and citrinin have been shown to produce acute renal damage. Although both substrates act on the proximal tubule in the rat, they affect different parts of that nephron segment. As with most nephrotoxicants, the mechanism(s) or subcellular target(s) for citrinin or chromate is unknown. The availability of methodology for isolation of functional membrane vesicles has afforded the opportunity to study the plasma membrane as a target for the effects of citrinin and chromate. Whether studied solely with in vitro conditions or after administration to the rat, chromate exhibited its primary action on the basolateral (BL) membrane vesicles. This was exhibited by a reduction in the p-aminohippurate (PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg, sc) there was a significant, but relatively modest, effect on glucose transport by brush border (BB) vesicles. Citrinin, when studied in vitro, inhibited PAH transport (BL vesicles), but had only equivocal effects on BB glucose transport. However, after pretreatment of the rats with citrinin (60 mg/kg, ip), both BL and BB membrane vesicle function was reduced markedly at 3 hr. By 16 hr, an overshoot had returned for both transport substrates, although the glucose overshoot was still significantly below control. These data demonstrate that both citrinin and chromate alter proximal tubular cell membrane function and do so relatively early after administration to the rat. This effect suggests that alteration of membrane function by these nephrotoxicants is an early, if not initiating, event in the production of acute tubular necrosis.
Ansari
R A
RA
Department of Pharmacology, College of Medicine, University of Nebraska Medical Center, Omaha 68198-6810.
Thakran
R S
RS
Berndt
W O
WO
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002840:Chromates / Q000633:toxicity*; D002953:Citrinin / Q000633:toxicity*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects; D017680:Potassium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism
D001786:Blood Glucose; D002840:Chromates; D017680:Potassium Compounds; D002953:Citrinin; C027373:potassium chromate(VI); D010130:p-Aminohippuric Acid