Lisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy

Abstract

Aims: To investigate the potential role of renalase in adriamycin nephropathy and the effect of lisinopril on the regulation of renalase. Methods: Adriamycin nephropathy was induced in male Wistar rats (n=12) by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model group or a treatment group, to which were administered distilled water or the angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks. Six normal rats served as controls. At the end of study, physiological parameters and systolic blood pressure were measured. Glomerulosclerosis and tubulointerstitial injury were assessed by histopathology Renalase protein expression in kidney was quantified by immunohistochemistry and immunoblotting. The serum concentration and urinary excretion of renalase were determined by enzyme-linked immunosorbent assay. Results: In model group rats, proteinuria and systolic blood pressure were elevated. Increased serum renalase concentration was observed; however, renalase protein expression in the kidney was significantly decreased. Compared with the model group, decreased proteinuria, lower systolic blood pressure, and fewer morphologic lesions were detected in the treatment group. Although levels of serum renalase were similar, accumulation of renalase in urine and kidney tissue increased notably in the treatment group compared with the model group. Conclusions: This study suggests that renalase may be involved in the process of adriamycin-induced renal injuries. Lisinopril may attenuate adriamycin-induced kidney injury by controlling blood pressure, which may be partially attributed to the renalase expression and secretion.

Effects of Renin-Angiotensin System Inhibitors on Renal Expression of Renalase in Sprague-Dawley Rats Fed With High Salt Diet

“…Han et al [19] were the first to demonstrate that the ACE inhibitor lisinopril markedly increased the expression of renalase in the kidney tissues of rats with adriamycin-induced nephropathy. More recently, Zhou et al [20] discovered that valsartan, an AT1R antagonist, promoted the stabilization of atherosclerotic plaque by increasing serum renalase and renalase expression in the fibrous cap of the atherosclerotic plaques in ApoE − / − mice fed with high-fat diet.…”

“…The renal RAS was identified and believed to be potentially associated with the regulation of renalase. RAS inhibitors were shown to upregulate renal-tissue and circulating renalase levels in rats with adriamycin-induced nephropathy and mice with high-fat intake [19,20]. Whether local RAS affects renal renalase expression under the high-salt condition is not understood.…”

Pharmacological targeting of GSK3β confers protection against podocytopathy and proteinuria by desensitizing mitochondrial permeability transition

“…If the glomerulus was normal, a score of 0 was given; if 0∼25% was affected, a score of 1 was given; 25∼50% was scored as 2; 50∼75% was scored as 3; and 75∼100% was scored as 4. A glomerulosclerosis index (GSI) was calculated by multiplying the number of glomeruli with a sclerosis score, and these values were summed and divided by the number of glomeruli assessed, including those with a sclerosis score of 0 (Han et al ., ; Liu et al ., ). The GSI for each kidney specimen was a sum of the points from 30 glomeruli.…”

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

“…17 Previous studies have also reported that Ang-II plays a key role in the process of ADR-induced nephrotoxicity. [18][19][20] However, studies have suggested that angiotensin-converting enzyme inhibitor 20 and angiotensin receptor blocker 18 exert a protective role against ADR-induced nephrotoxicity. 21,22 Ang-II is able to increase oxidative stress by stimulating the generation of both NO and NAD(P)H oxidase-derived superoxide, thereby enhancing reactive nitrogen species.…”