scholarly journals The Role of e-NOS in Chronic Cholestasis-Induced Liver and Renal Injury in Rats: The Effect of N-Acetyl Cysteine

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yusuf Gunay ◽  
Semsi Altaner ◽  
Nergiz Ekmen
Keyword(s):  
Liver Injury ◽  
Sham Group ◽  
Kidney Injury ◽  
Chronic Cholestasis ◽  
Liver And Kidney ◽  
Group A ◽  
Group B ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Introduction.The role of chronic cholestasis (CC) in liver injury and fibrosis remains unclear. The aims of this study were to define the role of endothelial nitric oxide synthase (e-NOS) in CC and the protective effect of N-acetyl-L-cysteine (NAC) in liver and kidney injury.Materials and Methods.Group A (sham group); Group B (CBDL); and Group C (CBDL + NAC). Group C received daily dosage of NAC (100 mg/kg) intraperitoneally for up to 4 weeks.Results.The rate of bridging fibrosis was higher (100% versus 20%,P=.025), but the intensity of e-NOS in liver was lower in rats that received NAC (1.3 versus 2.7,P=.046). The necrotic area in the kidneys among rats that received NAC was lower at week 4 (48% versus 57%;P<.001). The numbers of e-NOS stained cells in kidney were similar in sham group and the two groups with CBDL.Discussion.NAC reduced the stimulus for liver fibrosis in this rat model of CC and attenuated liver and kidney injury. Our study showed that e-NOS expression increased in liver tissue of rats with CC and that this was reversed by NAC. Treatment with NAC might restore e-NOS protein expression and prevent liver injury in CC.

The Effect of Pravastatin on Expression of Platelet-Derived Endothelial Nitric Oxide Synthase(eNOS) m-RNA and Atherosclerosis Course in Rabbits.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3881-3881
Author(s):  
Liping Ma ◽  
Mafei Kang ◽  
Songmei Yin ◽  
Danian Nie ◽  
Shuangfen Xi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Atherosclerotic Plaques ◽  
Microscopic Features ◽  
Enos Mrna ◽  
Group A ◽  
Normal Production ◽  
Group B ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Common Carotid Arteries

Abstract Objective To observe changes of platelet-derived endothelial nitric oxide synthesase(eNOS) mRNA expression in hypercholesterolemia( HC) and atherosclerosis( AS) rabbits, and relationship between these changes and atherosclerosis regression and reversion. To probe into mechanism of pravastatin on preventing and improving pathological courses of AS. Methods 30 male New Zealand White rabbits were divided randomly into three groups, 12 in group A, 12 in group B, and 6 in group C. All of them were fed with cholesterol-riched food (1g cholesterol,10g pig fat) daily during the first 12 weeks. In addition, in group A, pravastatin (10mg) was orally administered daily. At end of the 12th week, 6 of in group A and B were killed randomly and their aortas were removed and pathologic changes were studied, such as thickness of fatty-streaks or atherosclerotic plaques. In following 12 weeks, food enriched with cholesterol was stopped and substituted with normal food in all three groups. Treatment with pravastatin was continued in remaining members of group A. Pravastatin TX was initiated in remaining members of group B. No additional medicine was given to group C. At end 24th week, all of rabbits were killed and their aortas were examined for same pathologic changes as above. The expression of eNOS mRNA, NO, the activity of NOS and the level of serum lipids were measured at different times (0 week, 12th week and 24th week). Results 1. The expressions of platelet-derived eNOS mRNA(2–4×108 platelet /ml) The expressions in group A were 0.739±0.364,0.992±0.539,0.1.019±0.280 at 0, 12th, 24thweeks, respectively (difference not significant).The expressions in group B were 0.952±0.768,0.490±0.245,1.00±0.774 (reduced significantly at 12 week compared with 0 week(P<0.01), but increased at 24th week compared with 12th week(P<0.05). The expression in group C were 0.816±0.163,0.327±0.285,0.186±0.117 (reduced at 12th week and 24th week compared with 0 week(P<0.05 and P<0.01).It was reduced in B group and C group compared with group A at 12 week(P<0.05) and was increased in A group and B group compared with C group at 24 week(P<0.01). 2. Pathologic appearances of the arteries In group A, the intima was smooth and glossy in all of aortas at the 12th and 24th weeks. While in group B, there were a lot of yellow-gray fatty-streaks in tentire intima of all large arteries at the 12th week. The fatty-streaks in ascending aorta, aorta arch and thoracic aorta were thicker and larger than those in abdominal aorta and common iliac arteries. There were annular plaques at opening of coronary arteries and common carotid arteries, bulgied into the cavity at the 24th week. In group C, there were marked plaques in entire aorta at the 24th week. 3. Microscopic features The fatty-streaks or atherosclerotic plaques thicken measured in percentage of vessel wall, were 0.035±0.023,0.325±0.175,0.765±0.143 at 0,12th,24th, respectively. Greater in group C compared with group A and group B at 24 week(P<0.01). Conclusions The down-regulated expression of platelet-derived eNOS mRNA in HC or AS rabbits might be one of important causes in initiation and development of AS. Pravastatin can up-regulate expression of platelet-derived eNOS mRNA and NOS activity, and maintain normal production of NO. This leads to improvement of pathologic appearances or microscopic features of AS.

scholarly journals Role of Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis and Early Treatment of Acute Kidney Injury in a Case Series of Patients with Acute Decompensated Heart Failure: A Case Series

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Silvia Angeletti ◽  
Marta Fogolari ◽  
Davide Morolla ◽  
Federico Capone ◽  
Sebastiano Costantino ◽  
...  
Keyword(s):  
Early Treatment ◽  
Acute Decompensated Heart Failure ◽  
Case Series ◽  
Kidney Injury ◽  
Decompensated Heart Failure ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Group A ◽  
Group B ◽  
Neutrophil Gelatinase

Patients with acute decompensated heart failure (ADHF) frequently develop worsening in renal function until Acute Kidney Injury (AKI). The use of kidney injury biomarkers could be useful in the early diagnosis of AKI. In the present study, the role of the neutrophil gelatinase-associated lipocalin (NGAL), compared to the standard creatinine, in ADHF patients, was analyzed to evaluate if an early treatment could affect the outcome. A case series of 24 ADHF patients was enrolled and patients randomly divided in two groups (Group A and Group B). In Group A, NGAL, creatinine, and eGFR were measured, while in Group B, creatinine and eGFR alone were measured. NGAL was measured by turbidimetric immunoassay and creatinine using an enzymatic spectrophotometric method. In presence of AKI, creatinine increase and eGFR decrease were significantly lower in Group A than in Group B, whereas in absence of AKI the difference between the two groups was not significant. Hospitalization stay was significantly lower in Group A (receiving early treatment based on NGAL) than in Group B. In ADHF patients, plasma NGAL in combination with creatinine was superior to the standard creatinine in the diagnosis and early treatment of AKI with a better outcome and a decreased hospital stay.

scholarly journals Puerarin attenuates diabetic kidney injury through the suppression of NOX4 expression in podocytes

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Xueling Li ◽  
Weijing Cai ◽  
Kyung Lee ◽  
Bohan Liu ◽  
Yueyi Deng ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Therapeutic Benefit ◽  
Diabetic Kidney ◽  
Protein Levels ◽  
Napdh Oxidase ◽  
Radix Puerariae ◽  
Oxidative Effects ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract Radix puerariae, a traditional Chinese herbal medication, has been used to treat patients with diabetic nephropathy (DN). Several studies demonstrated that puerarin, the active compound of radix puerariae, reduces diabetic injury in streptozotocin (STZ)-induced diabetic rodent models. However, as STZ injection alone results in mild kidney injury, the therapeutic benefit afforded by puerarin in DN remained inconclusive. Thus we sought to clarify the role of puerarin by employing an accelerated DN model, STZ-induced diabetes in the endothelial nitric oxide synthase-null (eNOS−/−) mice. Puerarin treatment of diabetic eNOS−/− mice significantly attenuated albuminuria and diabetic kidney injury, which were associated with reduced oxidative stress and reduced NAPDH oxidase 4 (NOX4) in glomeruli of diabetic eNOS−/− mice. Puerarin treatment of murine podocytes culture in high glucose conditions led to reduced superoxide production and NOX4 expression. We further determined that that puerarin treatment increased both mRNA and protein levels of SIRT1 in podocytes and that puerarin led to SIRT1-mediated deacetylation of NF-κB and suppression of NOX4 expression. Our findings confirm the renoprotective effects of puerarin in an experimental model of advanced DN and provide a molecular mechanism by which puerarin exerts the anti-oxidative effects in podocytes  in the diabetic milieu.

Tissue Ki67 proliferative index expression and pathological changes in hemodialysis arteriovenous fistulae: Preliminary single-center results

2021 ◽  
pp. 112972982110154
Author(s):  
Raffaella Mauro ◽  
Cristina Rocchi ◽  
Francesco Vasuri ◽  
Alessia Pini ◽  
Anna Laura Croci Chiocchini ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Hot Spot ◽  
Wall Thickening ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Group A ◽  
The Mean ◽  
Set Up ◽  
Group B

Background: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. Materials and methods: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. Results: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0–65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 ( p = 0.001) and with NA ( p = 0.001). Conclusions: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.

scholarly journals High Basal Maximal Standardized Uptake Value (SUVmax) in Follicular Lymphoma Identifies Patients with a Low Risk of Long-Term Relapse

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2876
Author(s):  
Giovanni Manfredi Assanto ◽  
Giulia Ciotti ◽  
Mattia Brescini ◽  
Maria Lucia De Luca ◽  
Giorgia Annechini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Follicular Lymphoma ◽  
Standardized Uptake Value ◽  
Metabolic Tumor Volume ◽  
Late Relapse ◽  
Prognostic Role ◽  
Pet Ct ◽  
Group A ◽  
Group B

Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. Patients and Methods: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. Results: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. Conclusion: A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.

scholarly journals Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Natural Antioxidants ◽  
Sirtuin 1 ◽  
Potential Benefits ◽  
New Perspective ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.

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