Troxerutin down-regulates KIM-1, modulates p38 MAPK signaling, and enhances renal regenerative capacity in a rat model of gentamycin-induced acute kidney injury

2018 ◽  
Vol 9 (12) ◽  
pp. 6632-6642 ◽  
Author(s):  
Samir A. Salama ◽  
Hany H. Arab ◽  
Ibrahim A. Maghrabi
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
P38 Mapk ◽  
Tissue Regeneration ◽  
Rat Model ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Mapk Signaling ◽  
Regenerative Capacity

Troxerutin enhances renal tissue regeneration, improves renal function, and decreases renal tissue injury in gentamycin-treated rats.

scholarly journals Mesenchymal Stem Cells in Renal Function Recovery after Acute Kidney Injury: Use of a Differentiating Agent in a Rat Model

2011 ◽  
Vol 20 (8) ◽  
pp. 1193-1208 ◽  
Author(s):  
Gaetano La Manna ◽  
Francesca Bianchi ◽  
Maria Cappuccilli ◽  
Giovanna Cenacchi ◽  
Lucia Tarantino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Rat Model ◽  
Kidney Injury ◽  
Renal Function Recovery ◽  
Function Recovery ◽  
Differentiating Agent

scholarly journals Protection of Coenzyme Q-10 Against Contrast-induced Acute Kidney Injury in Diabetic Rats

2021 ◽  
Author(s):  
Sheila Marques Fernandes Couto ◽  
Cassiane Dezoti da Fonseca ◽  
Mirian Watanabe ◽  
Maria de Fátima Fernandes Vattimo
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Risk Factor ◽  
Coenzyme Q ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Renal Hemodynamics

Abstract Background: Diabetes Mellitus (DM) is a important risk factor for Contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI share oxidative damage and inflammation mechanisms that induction of protective and cellular adaptation enzymes as coenzyme Q-10 (COQ-10). The aim of this study was to investigate the therapeutic potential of COQ-10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats submitted to the CI-AKI model. Methods: Wistar rats, male, randomized into four groups: Citrate- control animals, received citrate buffer (streptozotocin vehicle, 0.4 ml); DM- animals that received streptozotocin (60 mg/kg); DM+IC: DM animals, treated with iodinated contrast (IC, 6 ml/kg); DM+IC+COQ-10: DM animals treated with COQ-10 (10 mg/kg) and that received with IC (6 ml/kg). The protocols lasted 4 weeks. Were evaluated the renal function by inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis.Results: DM animals showed reduced renal function which was reflected with an increase of serum creatinine and significant reduced of inulin clearance, as well as a reduction on RBF, increased RVR and redox imbalance with a higher urinary peroxides, nitrate lipid peroxidation levels and depletion of thiols in renal tissue. IC treatment exacerbated theses changes in DM + IC. COQ-10 administration ameliorates renal function, prevented hemodynamic changes, neutralize oxidative damage and progression of the histologic damage in the DM+IC+COQ-10 group. Conclusion: This study is the first that demonstrated a renoprotection of COQ-10 in experimental model of risk factor of DM for CI-AKI. COQ-10 presented an antioxidant effect on the CI-AKI in diabetic rats, by improving function and renal hemodynamics, preserving morphology and reducing oxidative stress.

Renoprotective Effects of Artesunate against Renal Ischemia-Reperfusion Injury in Rat Model

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Bassim I Mohammed ◽  
Najah R Hadi ◽  
Jabber Huda ◽  
Galal Elkilany ◽  
RB Singh
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Plasma Concentrations ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Control Group ◽  
Tissue Concentrations

Renal ischemia-reperfusion (Renal I/R) leads to acute kidney injury (AKI),a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models,both in vitro and in vivo,have been used to study the pathogenic mechanisms of ischemic AKI and to test reno-protective strategies. Aim: To study potential protective effects of artesunate on renal I/R injury. Renal I/R injury was unilaterally induced in adult (3 to 5 months) male Sprague-Dawely rats,whose weights ranged from 180 to 390 g. Thereafter,the animals were pre-treated with artesunate intra-peritoneally,and at the end of reperfusion sacrificed humanely. Plasma,serum and tissue samples were obtained for analysis. Plasma concentrations of NGAL (neutrophil gelatinase associated lipocalin),an iron-trafficking protein involved in multiple processes such as apoptosis,innate immunity and renal development,and tissue concentrations of IL-18 (Interleukin-18) were measured via ELISA analysis. Serum urea and creatinine were also measured in the samples. Artesunate improved renal ischemia reperfusion,including renal function and brought about reductions in inflammatory mediators and kidney tissue injury. Plasma concentrations of NGAL and tissue concentrations of IL-18 were significantly (p < 0.05) lower in the artesunatepretreated group than in the vehicle and control groups. Furthermore,serum concentrations of urea and creatinine were significantly (p < 0.05) decreased in the pretreated group as compared to the control group. Artesunate can significantly improve renal function following I/R through down-regulation of inflammatory parameters and NGAL expression. Furthermore,it could serve as a potential therapy in ischemia reperfusion-induced acute kidney injury.

scholarly journals Physical Training Is a Potential Modifier of Risk for Contrast-Induced Acute Kidney Injury in Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sheila M. F. Couto ◽  
Douglas I. Machado ◽  
Carolina Conde ◽  
Vinicius C. Silva ◽  
Adriana A. Souza ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Acute Kidney Injury ◽  
Blood Flow ◽  
Renal Function ◽  
Single Dose ◽  
Renal Blood Flow ◽  
Physical Training ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Renal Vascular

Background. Iodinated contrast (IC) is a leading cause of hospital-based acute kidney injury (AKI). Contrast-induced acute kidney injury (CI-AKI) is a decline in renal function due to iodinated contrast administration and occurs more frequently in individuals with increasingly common risk factors, such as diabetes mellitus (DM). Physical training (PT) can have renoprotective effects on CI-AKI in diabetic nephropathy. The aim of this study was to evaluate the injury in kidneys of diabetic rats submitted to treatment with IC, evaluating the impact of PT on hemodynamics and renal function in addition to oxidative profile in diabetic rats submitted to IC-AKI. Materials and Methods. Adult male Wistar rats are randomized into four groups: citrate ( n = 7 ): control group, citrate buffer (streptozotocin-STZ vehicle), intravenous tail (iv), single dose; DM ( n = 7 ): STZ, 60 mg/kg, iv, single dose; DM+IC ( n = 7 ): DM rats treated with IC (sodium meglumine ioxithalamate, 6 mL/kg, intraperitoneal (ip), single dose); DM+IC+PT ( n = 7 ): DM rats treated with IC as mentioned and submitted to physical training. Renal function parameters (inulin clearance, neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, and urinary albumin), hemodynamics (renal blood flow and renal vascular resistance), and oxidative profile (urinary peroxides, urinary TBARS, urinary nitric oxide, and renal tissue thiols) were evaluated. Results. It was possible to observe a decrease in inulin clearance, renal blood flow, and thiols in renal tissue accompanied by an increase in urinary flow, serum creatinine, urinary albumin, renal vascular resistance, urinary peroxides, urinary nitrate, and TBARS in the DM group compared to the citrate group. The DM+IC group showed a reduction in inulin clearance, and the renal dysfunction was also seen by the increased NGAL. Renal hemodynamics and oxidative profile compared were also worsened in the DM group. PT improved renal function by increasing renal blood flow and thiol levels in renal tissue and reduced renal vascular resistance, metabolites of reactive oxygen, nitrogen species, and lipid peroxidation in the DM+IC+PT group compared to DM+IC. Conclusions. Our results confirmed that DM induction increases renal vulnerability to the toxicity of IC and an association between DM with IC predisposes to severe AKI with reduced renal function alongside with renal hemodynamic alterations and oxidative mechanism of injury. The PT showed a renoprotective effect in DM animals subjected to damage with IC by modulating renal hemodynamics and oxidative profile, confirming a potential to modify the risk of CI-AKI when diabetes mellitus is present.

scholarly journals The combination of G-CSF and AMD3100 mobilizes bone marrow-derived stem cells to protect against cisplatin-induced acute kidney injury in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhi Chen ◽  
Xiang Ren ◽  
Ruimin Ren ◽  
Yonghong Wang ◽  
Jiwen Shang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Kidney Injury ◽  
Saline Group ◽  
Inflammatory Factors ◽  
Tissue Samples

Abstract Background Several studies have confirmed that mobilizing bone marrow-derived stem cells (BMSCs) ameliorates renal function loss following cisplatin-induced acute kidney injury (AKI). The aim of this study was to explore whether the combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor (AMD3100) exerts beneficial effects on renal function recovery in a model of cisplatin-induced nephrotoxicity. Methods C57BL/6J mice received intraperitoneal injections of G-CSF (200 μg/kg/day) for 5 consecutive days. On the day of the last injection, the mice received a single subcutaneous dose of AMD3100 (5 mg/kg) 1 h before cisplatin 20 mg/kg injection. Ninety-six hours after cisplatin injection, the mice were euthanized, and blood and tissue samples were collected to assess renal function and tissue damage. Cell mobilization was assessed by flow cytometry (FCM). Results Mice pretreated with G-CSF/AMD3100 exhibited longer survival and lower serum creatinine and blood urea nitrogen (BUN) levels than mice treated with only G-CSF or saline. Combinatorial G-CSF/AMD3100 treatment attenuated tissue injury and cell death, enhanced cell regeneration, and mobilized a higher number of stem cells in the peripheral blood than G-CSF or saline treatment. Furthermore, the mRNA expression of proinflammatory factors was lower, whereas that of anti-inflammatory factors was higher, in the G-CSF/AMD3100 group than in the G-CSF or saline group (all P < 0.05). Conclusions These results suggest that combinatorial G-CSF/AMD3100 therapy mobilizes BMSCs to accelerate improvements in renal functions and prevent cisplatin-induced renal tubular injury. This combinatorial therapy may represent a new therapeutic option for the treatment of AKI and should be further investigated in the future.

TLR2 and TLR4 play opposite role in autophagy associated with cisplatin-induced acute kidney injury

2018 ◽  
Vol 132 (16) ◽  
pp. 1725-1739 ◽  
Author(s):  
Magaiver Andrade-Silva ◽  
Marcos Antonio Cenedeze ◽  
Luiz Augusto Perandini ◽  
Raphael José Ferreira Felizardo ◽  
Ingrid Kazue Mizuno Watanabe ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Protective Role ◽  
Heme Oxygenase 1 ◽  
Protective Function ◽  
Autophagy Induction ◽  
Lower Expression

Acute kidney injury (AKI) is considered an inflammatory disease in which toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, the present study aimed to evaluate the specific participation of TLR2 and TLR4 molecules on the development of cisplatin-induced AKI. Complementarily, we also investigated the link between TLRs and heme oxygenase-1 (HO-1), a promisor cytoprotective molecule. First, we observed that only the absence of TLR2 but not TLR4 in mice exacerbated the renal dysfunction, tissue injury and mortality rate, even under an immunologically privileged microenvironment. Second, we demonstrated that TLR2 knockout (KO) mice presented lower expression of autophagy-associated markers when compared with TLR4 KO animals. Similar parameter was confirmed in vitro, using tubular epithelial cells derived from both KO mice. To test the cross-talking between HO-1 and TLRs, hemin (an HO-1 internal inducer) was administrated in cisplatin-treated TLR2 and TLR4 KO mice and it was detected an improvement in the global renal tissue parameters. However, this protection was less evident at TLR2 KO mice. In summary, we documented that TLR2 plays a protective role in cisplatin-induced AKI progression, in part, by a mechanism associated with autophagy up-regulation, considering that its interplay with HO-1 can promote renal tissue recover.

scholarly journals The Combination of G-CSF/AMD3100 Mobilizes Bone Marrow-Derived Stem Cells to Rescue Mice from Cisplatin-Induced Acute Kidney Injury

2021 ◽  
Author(s):  
Zhi Chen ◽  
Xiang Ren ◽  
Ruimin Ren ◽  
Yonghong Wang ◽  
Jiwen Shang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Bone Marrow Cells ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Kidney Injury ◽  
Inflammatory Factor ◽  
Tissue Samples

Abstract Background: Several studies have confirmed that mobilizing bone marrow-derived stem cells (BMSCs) ameliorates renal function loss following cisplatin-induced acute kidney injury (AKI). The aim of this study was to explore whether the combination of G-CSF/AMD3100 exerts beneficial effects with respect to renal function recovery in a mouse model of cisplatin-induced nephrotoxicity. Methods: C57BL/6J mice received intraperitoneal injections of G-CSF (200 μg/kg/d) for 5 consecutive days. On the day of the last injection, the mice received a single subcutaneous dose of AMD3100 (5 mg/kg) 1 hour before cisplatin 20 mg/kg injection. 96 hours after cisplatin injection, the mice were euthanized, blood and tissue samples were collected to assess renal function and tissue damage. Cell mobilization was assessed by flow cytometry. Results: Mice pretreated with G-CSF/AMD3100 exhibited longer survival and significantly lower serum creatinine and BUN levels than mice treated with only G-CSF or saline, exhibited attenuated tissue injury and cell death and enhanced tissue repair and cell regeneration. C57BL/6J mice pretreated with G-CSF/AMD3100 exhibited higher numbers of stem cells in peripheral blood than mice treated with only G-CSF or saline. Furthermore, G-CSF/AMD3100 administration prevented increases in the expression of proinflammatory factors, such as IL-6 and TNF-α, and increased the expression of the anti-inflammatory factor IL-10. Conclusions: These results suggest that G-CSF/AMD3100 mobilizes bone marrow cells to improve renal function and prevent cisplatin-induced renal tubular injury and that the combination of G-CSF/AMD3100 is superior to G-CSF alone for preventing AKI. This combination may represent a new therapeutic option for the treatment of AKI and warrants further investigation.

scholarly journals P0512SKLB023 ATTENUATED LIPOPOLYSACCHARIDE-INDUCED ACUTE KIDNEY INJURY VIA INHIBITION OF NF-KAPPPAB AND MAPKS PATHWAYS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Qian Ren ◽  
Liang Ma ◽  
Ping Fu
Keyword(s):  
Nitric Oxide ◽  
Acute Kidney Injury ◽  
Western Blot ◽  
Renal Dysfunction ◽  
P38 Mapk ◽  
Kidney Injury ◽  
Mapk Signaling ◽  
No Production ◽  
Lps Challenge ◽  
Anti Inflammatory

Abstract Background and Aims Excessive nitric oxide (NO) production by the activation of inducible nitric oxide synthase (iNOS) during sepsis was considered to contribute to acute kidney injury (AKI) and selective inhibition of iNOS activity may be a promising strategy for the treatment of sepsis-induced AKI. The novel small molecule compound (Z)-N-(3-Chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acet-amide (SKLB023) as a selective iNOS inhibitor was designed, synthesized by our lab and exhibited therapeutic potential in arthritis and non-alcoholic steatohepatitis models with potent anti-inflammatory effects. This study aimed to evaluate whether SKLB023 as a drug candidate could offer renal protective effect against sepsis-induced AKI. Method 21 C57BL6 mice (20-22g, 6-8 weeks old) were randomly divided into three groups: control, model, SKLB023 pretreatment. AKI was induced by a single injection of 10mg/kg LPS, and SKLB023 was orally administrated at the dose of 50 mg/kg for three consecutive days and one hour before LPS injection. All mice were sacrificed 16h after LPS injection and blood and kidney tissues were collected for further evaluation. LPS-induced renal dysfunction was assessed by measurement of blood creatinine and urea nitrogen (BUN) as well as histopathological changes. Moreover, the kidney mRNA and protein expression of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1(KIM-1), newly identified kidney injury markers, were tested by polymerase chain reaction (PCR) and western blot. To explore underlying mechanisms, the renal expression of inflammatory cytokine genes IL-1β, IL-6, mcp-1 and proteins iNOS, COX-2, IL-1β, TNF-α, IL-6, HMGB1 in were measured. The total expression of nuclear factor-kappa B (NF-κB), IκBα and MAPKs proteins (ERK1/2, p38 MAPK) and their corresponding phosphoproteins (p-NF-κB, p-IκBα, p-ERK1/2, p-P38 MAPK) in mice kidneys were subsequently analyzed by western blot. Results 16hours following LPS challenge, mice developed AKI as evidenced by elevated creatinine and BUN levels and corresponding pathological changes. Additionally, kidney expression of NGAL and KIM-1 were remarkably increased after LPS injection. SKLB023 pretreatment, however, alleviated LPS-induced renal dysfunction. Moreover, the excessive production of inflammatory cytokines during sepsis was significantly suppressed by SKLB023. Further observation from PCR and immunoblot results indicated that SKLB023 attenuated the activity of NF-kB and the phosphorylation of ERK1/2 and p38 MAPK in septic AKI mice. Conclusion These data demonstrated that SKLB023 exhibited renoprotective effect in LPS-induced AKI, which was associated with its anti-inflammatory activities by inhibiting the NF-kappaB and MAPK signaling pathways

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