Blanche Martin

Protective effect of nitric oxide in aristolochic acid‐induced toxic acute kidney injury: an old friend with new assets

What is the central question of this study? Despite the fact that the pathogenesis of aristolochic acid (AA) nephropathy is still unclear, we sought to determine whether nitric oxide is involved in the underlying mechanism of AA‐induced acute kidney injury (AKI). What is the main finding and its importance? Using a model of progressive tubulointerstitial nephritis, in which AA nephropathy exhibits two interconnected phases, an acute phase and a chronic phase of injury, we demonstrated that maintenance of nitric oxide bioavailability is essential to improve the outcome of AA‐induced AKI.

Restored nitric oxide bioavailability reduces the severity of acute-to-chronic transition in a mouse model of aristolochic acid nephropathy

Aristolochic Acid (AA) nephropathy (AAN) is a progressive tubulointerstitial nephritis characterized by an early phase of acute kidney injury (AKI) leading to chronic kidney disease (CKD). The reduced nitric oxide (NO) bioavailability reported in AAN might contribute to renal function impairment and progression of the disease. We previously demonstrated that L-arginine (L-Arg) supplementation is protective in AA-induced AKI. Since the severity of AKI may be considered a strong predictor of progression to CKD, the present study aims to assess the potential benefit of L-Arg supplementation during the transition from the acute phase to the chronic phase of AAN. C57BL/6J male mice were randomly subjected to daily i.p. injections of vehicle or AA for 4 days. To determine whether renal AA-induced injuries were linked to reduced NO production, L-Arg was added to drinking water from 7 days before starting i.p. injections, until the end of the protocol. Mice were euthanized 5, 10 and 20 days after vehicle or AA administration. AA-treated mice displayed marked renal injury and reduced NO bioavailability, while histopathological features of AAN were reproduced, including interstitial cell infiltration and tubulointerstitial fibrosis. L-Arg treatment restored renal NO bioavailability and reduced the severity of AA-induced injury, inflammation and fibrosis. We concluded that reduced renal NO bioavailability contributes to the processes underlying AAN. Furthermore, L-Arg shows nephroprotective effects by decreasing the severity of acute-to-chronic transition in experimental AAN and might represent a potential therapeutic tool in the future.

Evaluation of inducible nitric oxide synthase inhibition on kidney function and structure in high‐fat diet‐induced kidney disease

What is the central question of this study? The metabolic pathways regulating the effects of obesity on the kidney remain unknown. We sought to determine whether inducible nitric oxide synthase (iNOS) is involved in the underlying mechanisms of high‐fat diet‐induced kidney disease using a specific iNOS inhibitor, N6‐(1‐iminoethyl)‐l‐lysine hydrochloride (L‐NIL). What is the main finding and its importance? We did not demonstrate an upregulation of iNOS renal expression after high caloric intake, suggesting that iNOS might not be a crucial player in the development of obesity‐induced kidney disease. Although L‐NIL treatment clearly ameliorated systemic metabolic parameters, the effect on loss of renal function, impairment of tubular integrity, oxidative stress and inflammation appeared to be more moderate.

Evaluation of iNOS inhibition on kidney function and structure in high-fat diet-induced kidney disease.

What is the central question of this study? The metabolic pathways regulating the effects of obesity on the kidney remain unknown. We sought to determine whether inducible nitric oxide synthase (iNOS) is involved in the underlying mechanisms of high‐fat diet‐induced kidney disease using a specific iNOS inhibitor, N6‐(1‐iminoethyl)‐l‐lysine hydrochloride (L‐NIL). What is the main finding and its importance? We did not demonstrate an upregulation of iNOS renal expression after high caloric intake, suggesting that iNOS might not be a crucial player in the development of obesity‐induced kidney disease. Although L‐NIL treatment clearly ameliorated systemic metabolic parameters, the effect on loss of renal function, impairment of tubular integrity, oxidative stress and inflammation appeared to be more moderate.