Elevated cysteinyl leukotriene excretion in experimental glomerulonephritis.
The involvement of cysteinyl leukotrienes (LT) in the etiology of glomerulonephritis (GN) was investigated in a rat model of nephrotoxic serum nephritis in which renal function, morphology, LTC4 synthase activity and urinary cysteinyl LT excretion were monitored over seven days. Significant alterations in renal function and morphology were evident on day 1 in nephritic rats, with a 12% decline in creatinine clearance, a greater than three-fold increase in urinary protein excretion and histologic evidence of basement membrane thickening. Urinary LTC4 excretion in the nephritic rats was elevated at this time to 140 +/- 38 pg/hr (P < 0.01) compared to undetectable levels in control animals. On days 3 and 7, while proteinuria intensified and glomerular filtration remained depressed, LTC4 excretion declined 14% (NS) and 79% (P < 0.05), respectively. The temporal changes in urinary LTC4 excretion were paralleled by concomitant alterations in LTC4 synthase activity in renal cortical microsomes, where an 84% (P < 0.01) drop in enzyme activity occurred from day 1 to day 7 in the nephritic group. This data provides the first measurement of urinary cysteinyl LT excretion and altered LTC4 synthase activity in a model of experimental GN and supports an early role for LT's in the development of subsequent functional changes.
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire - Dorval, Canada.
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Petric
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Ford-Hutchinson
D000818:Animals; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007672:Kidney Cortex / Q000201:enzymology; D017997:Leukotriene C4 / Q000652:urine*; D017998:Leukotriene D4 / Q000652:urine*; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D017997:Leukotriene C4; D017998:Leukotriene D4; D017999:Leukotriene E4; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase