The effects of fumonisin B1 on several markers of nephrotoxicity in rats.
Rats were injected intraperitoneally with saline or fumonisin B1 (FB1) at doses of 7.5 and 10.0 mg FB1/kg for 4 days. For each day of dosing, 24-hr urine samples were collected and analyzed for creatinine and protein content and the enzymes gamma-glutamyl-transpeptidase, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Twenty-four hours after the last dose, animals were killed and kidneys removed for ion transport measurement and histopathology. Significant increases in urine volume and decreases in urine osmolality were observed in both FB1 dose groups. Creatinine excretion was decreased only in the 10 mg FB1/kg group on the final day of the study. Urine protein excretion was elevated in both treated groups and found to be due primarily to high-molecular-weight proteins indicative of increased glomerular permeability. Enzymuria, a marker of tubular cell damage, was also observed with increases in the urinary excretion of all three enzymes measured. In renal cortical slices tubular transport of the anion p-aminohippuric acid was reduced by 75-80% and cationic transport of tetraethylammonium was reduced by 40% in the FB1-treated animals. While these results suggest significant alterations in renal function, only minor histopathologic changes were observed in the kidneys of both dose groups. Results of the present study indicate that urine volume, proteinuria, enzymuria, and ion transport are sensitive indicators of early FB1-induced nephrotoxicity.
Suzuki
C A
CA
Toxicology Research Division, Food Directorate, H.P.B., Health Canada, Ottawa, Ontario.
Hierlihy
L
L
Barker
M
M
Curran
I
I
Mueller
R
R
Bondy
G S
GS
D000818:Animals; D015415:Biomarkers / Q000652:urine; D002274:Carcinogens, Environmental / Q000633:toxicity*; D003404:Creatinine / Q000652:urine; D004591:Electrophoresis, Polyacrylamide Gel; D005470:Fluorometry; D037341:Fumonisins; D005966:Glucuronidase / Q000652:urine; D007274:Injections, Intraperitoneal; D017136:Ion Transport / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000652:urine; D008297:Male; D008970:Molecular Weight; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009994:Osmolar Concentration; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine; D010130:p-Aminohippuric Acid / Q000652:urine
D015415:Biomarkers; D002274:Carcinogens, Environmental; D037341:Fumonisins; D009183:Mycotoxins; D013723:Teratogens; D013757:Tetraethylammonium Compounds; C056933:fumonisin B1; D019789:Tetraethylammonium; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; C033263:N-acetyl-beta-glucuronidase; D005966:Glucuronidase; D010130:p-Aminohippuric Acid