INHIBITION OF LEUKOTRIENE BIOSYNTHESIS IMPROVES RENAL-FUNCTION IN EXPERIMENTAL GLOMERULONEPHRITIS

The development of renal dysfunction in experimental glomerulonephriti s (GN) is mediated in part by enhanced leukotriene (LT) formation. In our studies the pathophysiological role of LTs was investigated throug h pharmacological inhibition of LT biosynthesis in a rat model of neph rotoxic serum nephritis. MK-0591, an indirect inhibitor of 5-lipoxygen ase activity, was co-administered to rats injected with nephrotoxic ra bbit serum, followed by assessment of renal function, morphology and m icrosomal LTC(4) synthase activity on day 7. A significant improvement in glomerular function was noted (p < 0.05), together with a 50% redu ction in proteinuria (p < 0.01) in animals receiving MK-0591 (60 mg kg (-1) day(-1)). In addition, the fall in renal LTC(4) synthase activity which occurred in nephritic rats (to 74% of control values, p < 0.01) was prevented in drug-treated animals. Based on these results, it app ears that inhibition of LT biosynthesis protects against both renal im pairment and alterations in LTC(4) synthase activity during the develo pment of experimental GN, and may provide a useful therapeutic adjunct in the treatment of this disease.