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Elevated cysteinyl leukotriene excretion in experimental glomerulonephritis
R Petric1, A W Ford-Hutchinson
1Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire - Dorval, Canada.
Kidney International
|November 1, 1994
Summary
Cysteinyl leukotrienes (LT) play an early role in experimental glomerulonephritis (GN). Urinary LT excretion and LTC4 synthase activity were measured in a rat model, revealing significant changes during disease progression.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Glomerulonephritis (GN) is a significant cause of kidney disease.
- The role of cysteinyl leukotrienes (LT) in GN pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the involvement of cysteinyl leukotrienes (LT) in the etiology of experimental glomerulonephritis (GN).
- To measure urinary cysteinyl LT excretion and LTC4 synthase activity in a rat model of nephrotoxic serum nephritis.
Main Methods:
- Rats with nephrotoxic serum nephritis were monitored for seven days.
- Renal function (creatinine clearance), urinary protein excretion, renal morphology, urinary cysteinyl LT excretion, and renal cortical LTC4 synthase activity were assessed.
Main Results:
- Nephritic rats showed impaired renal function and increased proteinuria from day 1.
- Urinary LTC4 excretion was elevated early in GN but declined over time.
- Renal cortical LTC4 synthase activity decreased significantly from day 1 to day 7 in nephritic rats.
Conclusions:
- Cysteinyl leukotrienes (LT) are involved early in the development of experimental glomerulonephritis (GN).
- Temporal changes in urinary LT excretion and LTC4 synthase activity correlate with GN progression.
- This study provides the first measurements of urinary cysteinyl LT and altered LTC4 synthase activity in experimental GN.