EFFECTS OF MEVALONATE PATHWAY MODULATORS UPON REACTIVITY OF MACROPHAGES IN E XPERIMENTAL NEPHROSCLEROSIS

Abstract

Abstract. The effects of cholesterol (Ch) diet, i.p. administration of mevalonic acid (Mev) and their combined application upon nitric oxide (NO) production in peritoneal macrophages, as well as upon biochemical characteristics of kidney function derangements, and histological parameters of tissue alterations, infiltration and fibrosis were studied in experimental model of chronic rhabdomyolysis-induced renal injury induced in C57Bl/6 mice. The effects of Ch diet, Mev and their combination on the degree of renal fibrosis were also studied in a model of unilateral ureteral obstruction. In normal animals, and, especially, in nephrotic mice, Ch diet was shown to cause a dramatic decrease of LPS-induced NO production, whereas Mev did enhance NO production significantly. Administration of Mev during Ch treatment abolished, in part, the suppressive effect of Ch. Ch diet was shown to enhance fibrotic response, without significant effect upon tissue alteration and mononuclear infiltration, whereas Mev enhanced alterative component and slightly diminished fibrosis. We conclude that Ch diet and Mev exert opposite effects upon the course and outcome of chronic nephropathy for their inhibitory (Ch) and stimulating (Mev) effect on mevalonate pathway, which is involved in the control of macrophage M1-M2 polarization.

Keywords

• nephrosclerosis
• macrophages
• cholesterol
• mevalonic acid
• nitric oxide