Inhibition of human renal acid phosphatases by nephrotoxic micromolar concentrations of fluoride.
Fluoride is considered to be a nephrotoxic substance, due to the association of 50-180 microM serum concentrations of fluoride with dose-related, subclinical to overt clinical renal impairment. At these concentrations the cellular targets of fluoride in renal tissue remain unknown. Fluoride at micromolar concentrations inhibits some enzymes including phosphatases. Here the effects of fluoride on a recently characterized acid phosphatase complex present only in a few human tissues were studied. This enzyme complex consists of alkaline fixation-resistant beta-glycerophosphatase and tartrate-resistant a-naphthyl phosphatase, and these are different from activities of known types of acid phosphatase and specific phosphatases. In kidney, strong activities for this complex are detected only in the endothelium of the afferent arterioles and in glomeruli. It appeared that alkaline fixation-resistant and lysosomal acid phosphatase activities were significantly inhibited in afferent arterioles and glomeruli by 75 microM fluoride. Tartrate-resistant activity was significantly inhibited by greater concentrations (250 microM). Inhibition of acid phosphatases in the afferent arterioles and glomeruli may be one renal target of fluoride nephrotoxicity. Although the physiological substrates of this acid phosphatase complex are unknown, its specific and restricted location may indicate a role in regulation of renal circulation.
Partanen
Seppo
S
Department of Pathology, Helsinki University Central Hospital, Jorvi Hospital, Espoo, Finland. seppo.partanen@hus.fi
D000135:Acid Phosphatase / Q000037:antagonists & inhibitors*; D000368:Aged; D000369:Aged, 80 and over; D001160:Arterioles / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005459:Fluorides / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D007678:Kidney Glomerulus / Q000201:enzymology; D008875:Middle Aged
D004791:Enzyme Inhibitors; D000135:Acid Phosphatase; D005459:Fluorides