Malate reduced kidney injury molecule (KIM-1) expression and selectively upregulated the renal nitric oxide production in obstructive nephropathy.

Abstract

Background: Malate, the tricarboxylic acid (TCA) cycle intermediary, upregulates renal nitric oxide (NO) signaling, and NO is renoprotective in nephropathy.

Objectives: This study explored the hypothesis that malate could increase renal NO and decrease renal injury and fibrotic markers in obstructive nephropathy.

Methods: Kidney injury was induced in rats via unilateral surgical ligation of the ureter, there after, rats were treated with malate (600 mg/kg, p.o.) for ten days. Urine was collected on days 0, 4, 7 and 10. Urinary sodium excretion was also determined. Western blot and biochemical analyses were carried on the nephropathic kidneys.

Results: Malate reduced kidney injury molecule (KIM-1) expression in the renal cortex and medulla of nephropathic rats (p < 0.05). NO production was selectively increased in the medulla of nephropathic rats treated with malate (58.3 ± 1.3 vs 77.8 ± 4.4 µM/ng, p < 0.05). Superoxide dismutase and catalase activity increased in the kidney of malate-treated nephropathic rats (p < 0.05). Transforming growth factor (TGF-β), an index of fibrosis, increased in the cortex but not medulla of the malate-treated UUO group. There was a consistent increase in collagenase activity in the cortex, and a reduction in the medulla.

Conclusion: Malate ameliorated the injury and inflammation but selectively reduced fibrosis in obstructive nephropathy (Fig. 6, Ref. 32). Text in PDF www.elis.sk Keywords: Malate, tricarboxylic acid cycle, nitric oxide, kidney injury molecule (KIM-1), obstructive nephropathy.