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To date there are no therapeutic strategies that limit the progression of Parkinson’s disease (PD). The mechanisms underlying PD-related nigrostriatal neurodegeneration remain incompletely understood, with multiple factors modulating the course of PD pathogenesis. This includes Nrf2-dependent gene expression, oxidative stress, α-synuclein pathology, mitochondrial dysfunction, and neuroinflammation. In vitro and sub-acute in vivo rotenone rat models of PD were used to evaluate the neuroprotective potential of a clinically-safe, multi-target metabolic and inflammatory modulator, the electrophilic fatty acid nitroalkene 10-nitro-oleic acid (10-NO2-OA). In N27A dopaminergic cells and in the substantia nigra pars compacta of rats, 10-NO2-OA activated Nrf2-regulated gene expression and inhibited NOX2 and LRRK2 hyperactivation, oxidative stress, microglial activation, α-synuclein modification and downstream mitochondrial import impairment. These data reveal broad neuroprotective actions of 10-NO2-OA in a sub-acute model of PD and motivate more chronic studies in rodents and primates.

Renal ischemia-reperfusion (I/R) causes acute kidney injury (AKI). Ischemic preconditioning (IPC) attenuates I/R-associated AKI. Whole body irradiation induces renal IPC in mice. Still, the mechanisms remain largely unknown. Furthermore, the impact of kidney-centered irradiation on renal resistance against I/R has not been studied. Renal irradiation (8.5 Gy) was done in male 8- to 12-wk-old C57bl/6 mice using a small animal radiation therapy device. Left renal I/R was performed by clamping the renal pedicles for 30 min, with simultaneous right nephrectomy, at 7, 14, and 28 days postirradiation. The renal reperfusion lasted 48 h. Following I/R, blood urea nitrogen (BUN) and serum creatinine (SCr) levels were lower in preirradiated mice compared with controls; so was the histological Jablonski score of AKI. The metabolomics signature of renal I/R was attenuated in preirradiated mice. The numbers of proliferating cell nuclear antigen (PCNA)-, cluster of differentiation molecule 11b (CD11b)-, and cell surface glycoprotein F4/80-positive cells in the renal parenchyma post-I/R were reduced in preirradiated versus control groups. Such IPC was significantly observed as early as

Nitrated fatty acids (NO2-FA) are an endogenous class of signaling mediators formed mainly during digestion and inflammation. The signaling actions of NO2-FA have been extensively studied, but their detection and characterization lagged. Several different nitrated fatty acid species have been reported in animals and humans, but their formation remains controversial, and a systemic approach to define the endogenous pool of NO2-FA is needed. Herein, we screened for endogenous NO2-FA in urine from healthy human volunteers as this is the main excretion route for NO2-FA and its metabolites, and it provides an excellent matrix for evaluation. Only isomers of two fatty acids, conjugated linoleic and linolenic acid were found to be nitrated. Several, previously unknown, nitrated species were identified and confirmed using high-resolution mass spectrometry, fragmentation analysis, and compared to synthetic nitrated standards, the main group corresponding to nitrated conjugated linolenic acid (NO2-CLnA). In contrast, we were unable to confirm the presence of previously reported nitrated omega-3's, oleic acid, arachidonic acid and α- and γ-linolenic acid, suggesting that their biological formation and presence in humans should be re-evaluated. Metabolite analysis of NO2-CLnA in human urine identified cysteine adducts and β-oxidation products, which were compared to the metabolic products of nitrated standards obtained using primary mouse hepatocytes. Importantly, NO2-CLnA isomers belong to two defined groups, are electrophilic, participate in Michael addition reactions and account for 39% of total urinary NO2-FA, highlighting their relative abundance and possible role in cell signaling.

AMP-activated protein kinase (AMPK) activation promotes early stages of epithelial junction assembly. AMPK activation in MDCK renal epithelial cells facilitates localization of the junction-associated proteins aPKCζ and Par3 to the plasma membrane and promotes conversion of Cdc42, a key regulator of epithelial polarization and junction assembly, to its active GTP bound state. Furthermore, Par3 is an important regulator of AMPK-mediated aPKCζ localization. Both aPKCζ and Par3 serve as intermediates in AMPK-mediated junction assembly, with inhibition of aPKCζ activity or Par3 knockdown disrupting AMPK’s ability to facilitate zonula occludens (ZO-1) localization. AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the tight-junction protein zonula occludens-1. Afadin is phosphorylated at two critical sites, S228 (residing within an aPKCζ consensus site) and S1102 (residing within an AMPK consensus site), that are differentially regulated during junction assembly and that exert different effects on the process. Expression of phospho-defective mutants (S228A and S1102A) perturbed ZO-1 localization to the plasma membrane during AMPK-induced junction assembly. Expression of S228A increased the ZO-1/afadin interaction, while S1102A reduced this interaction during extracellular calcium-induced junction assembly. Inhibition of aPKCζ activity also increased the ZO-1/afadin interaction. Taken together, these data suggest that aPKCζ phosphorylation of afadin terminates the ZO-1/afadin interaction and thus permits the later stages of junction assembly.

Aim Dual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response, with a putative role in angiogenesis. Modulating inflammation and perfusion contributes to renal conditioning against ischemia/reperfusion (I/R). We postulate that the functional loss of DUSP3 is associated with kidney resistance to I/R. Methods Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal I/R (30min/48h). Renal injury was assessed based on serum levels of urea (BUN) and Jablonski score. The expression of CD31 and VEGF vascular markers was quantified by RT-qPCR and immuno-staining. Renal resistivity index (RRI) was measured in vivo by Doppler ultrasound. Comparative phosphoproteomics was conducted using IMAC enrichment of phosphopeptides. Inflammatory markers were quantified at both mRNA and protein levels in ischemic vs. non-ischemic kidneys in WT versus Dusp3-/- . Results At baseline, we located DUSP3 in renal glomeruli and endothelial cells. CD31-positive vascular network was significantly larger in Dusp3-/- kidneys compared to WT, with a lower RRI in Dusp3-/- mice. Following I/R, BUN and Jablonski score were significantly lower in Dusp3-/- vs. WT mice. Phosphoproteomics highlighted a down-regulation of inflammatory pathways and up-regulation of phospho-sites involved in cell metabolism and VEGF-related angiogenesis in Dusp3-/- vs. WT ischemic kidneys. Dusp3-/- ischemic kidneys showed decreased mRNA levels of CD11b, TNF-α, KIM-1, IL-6, IL-1β and caspase-3 compared to controls. The numbers of PCNA-, F4-80- and CD11b-positive cells were reduced in Dusp3-/- vs. WT kidneys post I/R. Conclusion Genetic inactivation of Dusp3 is associated with kidney conditioning against I/R, possibly due to attenuated inflammation and improved perfusion.

OBJECTIVES: Obesity and non-alcoholic fatty liver diseases (NAFLD) are multifactorial diseases that affect more than 35% of the world's population. Fish oil (FO) is an important dietary component that provides essential omega-3 fatty acids (Ω-3) effective for hypertriglyceridemia with eicosapentaenoic acid shown to reduce cardiovascular and metabolic syndrome-related events. However, the mechanisms involved in these beneficial activities are still unclear. A metabolomic study of healthy volunteers receiving Lovaza, an omega-3-drug, showed a large increase in plasma and urinary metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). Moreover, in the diet-induced obesity (DIO) mouse model, CMPF was protective and reversed steatosis. We identified furan fatty acids (FuFA) present both in FO and Lovaza (0.1–1%) as the sources of CMPF and hypothesised that they were responsible for these beneficial effects. METHODS: We synthesized one FuFA and confirmed its structure by NMR and mass spectrometry and tested whether it had protective effects in this DIO model (23 weeks, 60 kcal% fat). After 16 weeks of the diet, FuFA (25mg/kg/day) was administered by gavage for the last 7 weeks. A glucose tolerance test was performed at week 4(th). Tissues and blood were collected at week 7(th) after 5h fasting. Mass spectrometry, ELISA, and multiplex analysis were performed on plasma. Liver staining (H&E) was also performed to quantify steatosis and ballooning. RESULTS: The glucose tolerance test showed improved glucose clearance in FuFA-treated mice compared to vehicle. The fasting level of insulin and c-peptide 2 were respectively 2.9- and 1.5-fold lower in FuFA- compared to the vehicle-treated mice. Additionally, circulating TNF-α was significantly lower (1.6-fold) in FuFA-treated mice. NAFLD activity scores - hepatocytes ballooning and steatosis - were also significantly decreased in FuFA-treated mice by 1.6- and 1.4-fold, respectively. Finally, an MS-based analysis of plasma showed a significant decrease in cholesterol (1.2-fold) and cholesterol-ester (1.4-fold) levels in FuFA-treated mice. CONCLUSIONS: In conclusion, the beneficial effects observed in Ω-3 and FO treatment on DIO and NAFLD may be related to the presence of FuFA in these dietary preparations. FUNDING SOURCES: NIH.

Background and Aims Whole-body irradiation has been suggested to induce renal ischemic preconditioning (RIP) in rodent models, possibly via neo-angiogenesis. First, we comprehensively investigate the pathways involved in kidney-centered irradiation. Next, we assess the functional and structural impact of kidney-centered irradiation applied before ischemia/reperfusion (I/R) injury. Finally, we test whether Sunitinib-mediated inhibition of the neo-angiogenesis prevents irradiation-associated RIP. Method Experiment 1: Unilateral irradiation of the left kidney (8.56 Gy) was performed in male 10-week-old wild-type C57bl/6 mice (n=10). One month later, total kidney RNA was extracted from irradiated and control (n=5) mice for comparative high-throughput RNA-Seq (using BaseSpace Sequence Hub Illumina). Functional enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Experiment 2: Two x-ray beams (225Kv, 13mA) specifically targeted both kidneys for a total dose of 8.56Gy. The right kidneys were removed and harvested, and the left kidneys undergo 30-minute ischemia followed by 48-hour reperfusion (n=8) at Days 7-14-21-28 post irradiation. Experiment 3: Following the same protocol of renal I/R at Day14, 3 groups of male 10-week-old wild-type C57bl/6 mice were compared (n=8 per group): 1/ bilateral pre-irradiation; 2/ bilateral pre-irradiation and gavage with Sunitinib from Day2 to Day13; 3/ control group without irradiation or gavage. Results Experiment 1: Comparative transcriptomics showed a significant up-regulation of various signaling pathways, including angiogenesis (HMOX1) and stress response (HSPA1A, HSPA1B). Expressions of angiogenesis markers (CD31, TGFb1, HMOX1) showed an increase at both mRNA (real-time qPCR) and protein (immuno-staining) levels in irradiated kidneys compared to controls (p Experiment 2: Following I/R, the blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly lower in the irradiated animals compared to controls: (BUN: 86.2±6.8 vs. 454.5±27.2mg/dl; SCr: 0.1±0.01 vs. 1.7±0.2mg/dl, p Experiment 3: One-way analysis of variance followed by Tukey’s test showed that, following I/R, the serum levels of BUN and SCr were lower in irradiated group compared to controls (BUN: 106.1±33.6 vs. 352.2±54.3mg/dl; SCr: 0.3±0.13 vs. 1±0.2mg/dl), and in irradiated group compared to the irradiated-exposed group to Sunitinib (BUN: 106.1±33.6 vs. 408.4±54.9mg/dl; SCr: 0.3±0.12 vs. 1.5±0.3mg/dl; p Conclusion Renal irradiation induces the activation of signaling pathways involved in angiogenesis in mice. Renal pre-irradiation leads to RIP, with preserved renal function and attenuated inflammation post I/R. Exposure to the anti-angiogenic drug Sunitinib post-irradiation prevents the irradiation-induced RIP.

Background and Aims Dual Specificity Phosphatase 3 (DUSP3) is a positive regulator of the innate immune response in case of sepsis, but its role in the ischemic damage is unknown. Here, we study (i) whether and where DUSP3 is expressed in the renal parenchyma, and (ii) whether its genetic deletion in Dusp3 systemic knock-out (Dusp3-/-) mice attenuates the I/R-associated inflammation and injury. Method Experiment 1: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal ischemia for 30 minutes followed by a reperfusion of 48 hours. Blood and kidneys were collected. Renal function was assessed upon I/R biomarkers, i.e. blood urea nitrogen (BUN) and creatinine (SCr). Expressions of inflammatory and immune markers were comparatively quantified at both mRNA (real-time qPCR) and protein (immuno-blotting and –staining) levels in ischemic vs. non-ischemic kidneys in Dusp3 WT vs. KO mice. Experiment 2: Ten C57BL/6 male WT and Dusp3-/- mice were anesthetized. Renal Doppler ultrasound was performed to assess the renal resistivity index (RRI). The expression of CD31 and VEGF vascular markers was quantified by the means of real-time qPCR and and immuno-staining (FiJi software). Results Experiment 1: An immuno-reactive signal for DUSP3 was detected in the glomeruli (in co-localization with nephrin) and in Meca-32-positive endothelial cells of both outer and inner medulla of mouse non-ischemic WT kidneys. No significant immunoreactivity for DUSP3 was detected in Dusp3-/- kidneys. Following renal I/R, the mRNA level of Dusp3 was increased 1.8-fold compared to baseline (p Experiment 2: The RRI non-invasively measured by ultrasound was lower in Dusp3-/- group compared to controls (0.56± 0.03 vs. 0.66±0.02; p Conclusion The genetic deletion of DUSP3 is associated with (i) increased renal vascular density, (ii) decreased RRI and (iii) nephroprotection against renal I/R injury.

Introduction L’irradiation corporelle induit un conditionnement ischemique renal (CIR) chez la souris. Les mecanismes cellulaires sont meconnus, hormis un possible role de la neo-angiogenese. Description Dans cette etude, nous etudions les voies impliquees dans l’irradiation renale. Ensuite, nous analysons l’impact fonctionnel sur les reins avant ischemie renale/reperfusion (I/R). Enfin, nous testons si l’inhibition de l’angiogenese par le Sunitinib empeche le CIR associe a l’irradiation. Methodes Exp1. Une irradiation renale(8 Gy) est realisee chez des C57bl/6 mâles (n = 10). Un mois plus tard, l’ARN renal total est extrait pour un RNAseq comparatif. Exp2. A 7–14–28 jours post-irradiation renale, les reins droits sont nephrectomises et les reins gauches subissent une ischemie (30 min)/reperfusion (48 h) (n = 8/timing). Exp3. Suivant le meme protocole d’I/R a j14, 3 groupes sont compares (n = 8/groupe) : – irradiation ; – irradiation et gavage au sunitinib de j2 a j13 ; – groupe temoin sans irradiation ni gavage. Resultats Exp1. RNAseq montre une up-regulation des voies de l’angiogenese. L’expression de VEGF et CD31 est significativement augmentee au niveau ARNm et proteique dans les reins irradies. Exp2. Apres I/R a j14 post-irradiation, les taux seriques d’uree (BUN) et de creatinine (SCr) sont plus faibles chez les souris irradiees par rapport aux temoins (BUN : 86,2 ± 6,8 vs 454,5 ± 27,2 mg/dL ; SCr : 0,1 ± 0,01 vs 1,7 ± 0,2 mg/dL, p Fig. 1 ). Conclusion L’irradiation renale induit l’activation de l’angiogenese chez la souris et est associee a un CIR, avec fonction renale preservee et inflammation attenuee post-I/R. L’exposition au sunitinib post-irradiation empeche ce CIR.

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch toward anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting in a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

Introduction L’irradiation corporelle a ete associee a un pre-conditionnement ischemique renal chez la souris. Les mecanismes de ce processus sont inconnus. Description Nous analysons l’impact fonctionnel et structurel de la radiotherapie centree sur les reins avant une ischemie renale/reperfusion (I/R). Methodes Experience 1 : sous anesthesie, 2 faisceaux de rayons X (225 Kv, 13 mA) ciblent specifiquement les reins pour une dose totale de 8,56 Gy. Trente jours plus tard, une nephrectomie droite est realisee et une ischemie du rein gauche est induite pendant 30 min. Apres 48 h de reperfusion, le rein gauche et le sang sont preleves (n = 6). Un groupe temoin (n = 6) subit une I/R renale sans irradiation. Experience 2 : une irradiation unilaterale des reins gauches (8,56 Gy) est realisee (n = 11). Trente jours plus tard, le rein gauche est preleve. Le rein gauche de souris non irradiees (n = 5) est utilise comme controle. L’ARN des reins irradies et controles est extrait pour une transcriptomique comparative (via DAVID program). Resultats A la suite d’une I/R renale, le taux d’uree etait significativement plus bas chez les animaux pre-irradiees (148 ± 93 mg/dL), comparativement aux controles (496 ± 33 ; p Conclusion L’irradiation renale induit un pre-conditionnement ischemique chez la souris, avec preservation de la fonction renale et attenuation de l’inflammation post-I/R. Les voies de signalisation susmentionnees pourraient participer a la resistance renale a l’I/R.

Lithium (Li) is the mainstay pharmacotherapeutic mood stabilizer in bipolar disorder. Its efficacious use is complicated by acute and chronic renal side effects, including nephrogenic diabetes insipidus (NDI) and progression to chronic kidney disease (CKD). The nuclear factor erythroid-derived 2–related factor 2 (Nrf2) pathway senses and coordinates cellular responses to oxidative and electrophilic stress. Here, we identify that graded genetic activation of Nrf2 protects against Li-induced NDI (Li-NDI) and volume wasting via an aquaporin 2–independent mechanism. Renal Nrf2 activity is differentially expressed on functional segments of the nephron, and its activation along the distal tubule and collecting duct directly modulates ion transporter expression, mimicking paradoxical effects of diuretics in mitigating Li-NDI. In addition, Nrf2 reduces cyclooxygenase expression and vasoactive prostaglandin biosynthesis. Pharmacologic activation of Nrf2 confers protective effects, confirming this pathway as a potentially novel druggable target for the prevention of acute and chronic renal sequelae of Li therapy.

Tight junctions (TJ) play an essential role in the epithelial barrier. By definition, TJ are located at the demarcation between the apical and baso-lateral domains of the plasma membrane in epithelial cells. TJ fulfill two major roles: (i) TJ prevent the mixing of membrane components; and (ii) TJ regulate the selective paracellular permeability. Disruption of TJ is regarded as one of the earliest hallmarks of epithelial injury, leading to the loss of cell polarity and tissue disorganization. Many factors have been identified as modulators of TJ assembly/disassembly. More specifically, in addition to its role as an energy sensor, adenosine monophosphate-activated protein kinase (AMPK) participates in TJ regulation. AMPK is a ubiquitous serine/threonine kinase composed of a catalytic α-subunit complexed with regulatory β-and γ-subunits. AMPK activation promotes the early stages of epithelial TJ assembly. AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the TJ-associated protein zonula occludens (ZO)-1, thereby facilitating ZO-1 distribution to the plasma membrane. In the present review, we detail the signaling pathways up-and down-stream of AMPK activation at the time of Ca2+-induced TJ assembly.

Background. Mesenchymal stromal cells (MSC) are fibroblast-like multipotent cells capable of tissue-repair properties. Given the essentiality of tight junctions (TJ) in epithelial integrity, we hypothesized that MSC modulate TJ formation, via the AMP-activated kinase (AMPK) pathway. Liver kinase-β1 (LKB1) and Ca2+-calmodulin-dependent protein kinase kinase (CaMKK) represent the main kinases that activate AMPK.Methods. The in vitro Ca2+switch from 5 μM to 1.8 mM was performed using epithelial Madin-Darby canine kidney (MDCK) cells cultured alone or cocultured with rat bone marrow-derived MSC or preexposed to MSC-conditioned medium. TJ assembly was measured by assessing ZO-1 relocation to cell-cell contacts. Experiments were conducted using MDCK stably expressing short-hairpin-RNA (shRNA) against LKB1 or luciferase (LUC, as controls). Compound STO-609 (50 μM) was used as CaMKK inhibitor.Results. Following Ca2+switch, ZO-1 relocation and phosphorylation/activation of AMPK were significantly higher in MDCK/MSC compared to MDCK. No difference in AMPK phosphorylation was observed between LKB1-shRNA and Luc-shRNA MDCK following Ca2+switch. Conversely, incubation with STO-609 prior to Ca2+switch prevented AMPK phosphorylation and ZO-1 relocation. MSC-conditioned medium slightly but significantly increased AMPK activation and accelerated TJ-associated distribution of ZO-1 post Ca2+switch in comparison to regular medium.Conclusions. MSC modulate the assembly of epithelial TJ, via the CaMKK/AMPK pathway independently of LKB1.

Mesenchymal stromal cells (MSC) have been demonstrated to attenuate renal ischemia/reperfusion (I/R) damage in rodent models. The mechanisms of such nephro-protection remain largely unknown. Furthermore, the optimal timing of MSC administration has been poorly investigated. Here, we compare the impact of MSC injection 7 days before (MSCD − 7) versus 1 day after (MSCD + 1) renal I/R in rats. Control groups received equivalent volumes of saline at similar time-points (SD − 7 and SD + 1). Right nephrectomy was performed, and left renal ischemia lasted 45 min. After 48-hour reperfusion, we observed significantly improved renal function parameters, reduced apoptotic index and neutrophil/macrophage infiltration in kidney parenchyma, and lower expression of tubular damage markers and pro-inflammatory cytokines in MSCD − 7 in comparison to MSCD + 1 and saline control groups. Next, comparative high-throughput RNA sequencing of MSCD − 7 vs. SD − 7 non-ischemic right kidneys highlighted significant down-regulation of fatty acid biosynthesis and up-regulation of PPAR-α pathway. Such a preferential regulation towards lipid catabolism was associated with decreased levels of lipid peroxidation products, i.e. malondialdehyde and 4-hydroxy-2-nonenal, in MSCD − 7 versus SD − 7 ischemic kidneys. Our findings suggest that MSC pretreatment may exert protective effects against renal I/R by modulating lipid metabolism in rats.

Introduction De recentes etudes experimentales et cliniques suggerent un effet nephroprotecteur des cellules stromales mesenchymateuses (CSM) lors d’une ischemie/reperfusion (I/R) renale. Neanmoins, les parametres d’administration des CSM, tels que le nombre, le site et le moment d’injection, restent debattus. Ainsi, chez le rongeur, les CSM auraient un effet benefique lors d’une injection avant l’I/R renale, mais seraient deleteres lors d’une administration a posteriori. Materiels et methodes Afin de preciser l’impact du moment d’administration de CSM sur la fonction renale lors d’une I/R, nous avons reparti des rats Lewis âges de 10 semaines en 4 groupes : les groupes 1 (CSM j-7, n = 10) et 2 (CSM j + 1, n = 10) ont recu une injection IV de CSM (1,5 × 106 dans 1 mL de liquide physiologique) respectivement 7 jours avant ou 1 jour apres l’I/R renale. Les groupes temoins 3 (LP j − 7, n = 6) et 4 (LP j + 1, n = 6) ont recu un volume equivalent de liquide physiologique au moment correspondant. L’ischemie renale gauche etait provoquee par clampage du pedicule vasculaire durant 45 minutes. Une nephrectomie droite etait pratiquee simultanement. Le prelevement sanguin etait realise 48 heures apres la reperfusion renale. La nature des CSM a ete confirmee par cytometrie en flux pour les marqueurs de surface usuels. Resultats Dans les groupes 1 et 3, les valeurs de creatininemie (SCr) etaient de 1,4 ± 0,7 versus 2,4 ± 0,8 mg/dL, respectivement ( p p Discussion L’administration de CSM 7 jours avant une I/R renale semble attenuer les lesions en comparaison a : – l’injection de liquide physiologique ; – l’injection de CSM apres l’I/R. Bien plus, l’administration de CSM apres l’I/R renale aggraverait l’insuffisance renale aigue. Conclusion En conclusion, le moment d’administration des CSM lors d’une I/R renale influence significativement leur effet, benefique ou deletere, sur la fonction renale.