scholarly journals Immunohistochemical Aspects of Cell Death in Diabetic Nephropathy

2016 ◽  
Vol 54 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Elena Bălăşescu ◽  
Mirela Cioplea ◽  
Alice Brînzea ◽  
Roxana Nedelcu ◽  
Sabina Zurac ◽  
...  
Keyword(s):  
Cell Death ◽  
Diabetic Nephropathy ◽  
Renal Tissue ◽  
Ultrastructural Changes ◽  
Control Group ◽  
Caspase 9 ◽  
Tissue Samples ◽  
Diabetic Kidney ◽  
Variable Expression ◽  
Positive Immunostaining

Introduction. Diabetes Mellitus causes ultrastructural changes triggered by partially clarified cellular mechanisms. Since cell death is an important mechanism in the appearance and progression of diabetic nephropathy, we studied alteration of several markers of apoptotic pathways signaling in renal tissue of diabetic or prediabetic patients. Methods. We analyzed 48 human kidney tissue samples divided into two study groups: the research group (43 renal tissue samples from diabetic or prediabetic patients), and the control group (5 renal tissue samples from patients without diabetes). Immunohistochemistry revealed expression of Bcl-2, APAF-1, CD-95 and Caspase-9 in the renal cortical structures. Statistical analysis was also performed (significance level P<0.05). Results. We found a variable expression of the antiapoptotic Bcl-2 with a decrease of Bcl-2 expression in diabetes. The control samples render evident intensely positive immunostaining for CD-95. In diabetes and diabetic nephropathy, there was positive immunostaining for APAF-1 at tubular cell level. Nuclear and cytoplasmic positivity for Caspase-9 was more frequently recorded as kidney damage progresses. APAF-1 and Caspase-9 positivity are arguments for an intrinsic apoptotic mechanism of cell death in diabetic nephropathy. Conclusion. The mechanisms of apoptotic cell death identified in diabetic kidney samples prove that Bcl-2, CD-95, APAF-1 and Caspase-9 represent reliable markers of cell death in human renal tissue. Our results support the hypothesis that apoptosis is a pathogenic and initiator mechanism of renal remodeling in diabetic kidney disease.

scholarly journals Caspases, Cell Death and Diabetic Nephropathy

2015 ◽  
Vol 53 (4) ◽  
pp. 296-303 ◽  
Author(s):  
Elena Bălăşescu ◽  
Daniela Adriana Ion ◽  
Mirela Cioplea ◽  
Sabina Zurac
Keyword(s):  
Cell Death ◽  
Diabetic Nephropathy ◽  
Cell Injury ◽  
Relative Proportion ◽  
Cysteine Proteases ◽  
Renal Tissue ◽  
World Health ◽  
Ultrastructural Changes ◽  
Number Of Patients ◽  
Health Organization

Abstract Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes. Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated. Caspases. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.

Oxidative Stress Is Associated With Cell Death, Wall Degradation, and Increased Risk of Rupture of the Intracranial Aneurysm Wall

Neurosurgery ◽  
2012 ◽  
Vol 72 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Elisa Laaksamo ◽  
Riikka Tulamo ◽  
Arto Liiman ◽  
Marc Baumann ◽  
Robert M. Friedlander ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Caspase 9 ◽  
Tissue Samples ◽  
Aneurysm Wall ◽  
Increased Risk ◽  
Risk Of Rupture ◽  
High Oxidative Stress

Abstract BACKGROUND: The cause of rupture of intracranial aneurysms (IA) is not well understood. We previously demonstrated that loss of cells from the IA wall is associated with wall degeneration and rupture. OBJECTIVE: To investigate the mechanisms mediating cell death in the IA wall. METHODS: Snap-frozen tissue samples from aneurysm fundi were studied with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunostaining (14 unruptured and 20 ruptured), as well as with Western blot (12 unruptured and 12 ruptured). RESULTS: Ruptured IA walls had more TUNEL-positive cells than unruptured walls (P &lt; .001). Few cells positive for cleaved caspase-3 were detected. Cleaved caspase-9 (intrinsic activation of apoptosis) was significantly increased in ruptured IA walls, whereas cleaved caspase-8 (extrinsic activation of apoptosis) was not detected. Increased expression of hemeoxygenase-1, a marker for oxidative stress, was associated with IA wall degeneration and rupture. CONCLUSION: Our results show that programmed cell death is activated in the IA wall via the intrinsic pathway. High oxidative stress in the IA wall is probably a significant cause of the intrinsic activation of cell death.

scholarly journals Renoprotective Effect of Fucoidan from Seaweed Sargassum angustifolium C. Agardh 1820 on Gentamicin-Induced Nephrotoxicity: From Marine Resources to Therapeutic Uses

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Khalil Pourkhalili ◽  
Zeinab Karimi ◽  
Mohammad Reza Farzaneh ◽  
Elham Ehsandoost ◽  
Mehdi Mohammadi ◽  
...  
Keyword(s):  
Urine Volume ◽  
Renal Tissue ◽  
Sulfated Polysaccharides ◽  
Control Group ◽  
Sod Activity ◽  
Tissue Samples ◽  
Therapeutic Uses ◽  
Male Wistar Rats ◽  
Sargassum Angustifolium ◽  
First Time

Background: Nephrotoxicity is a major side effect of aminoglycoside antibiotics, caused by oxidative damage and inflammation. Fucoidan, a group of sulfated polysaccharides derived from different species of brown algae, are well recognized for their antioxidant and anti-inflammatory activities. Objectives: In the present study, we aimed to investigate, for the first time, the efficacy of fucoidan extracted from Sargassum angustifolium C. Agardh 1820 against gentamicin-induced nephrotoxicity in rats. Methods: Twenty-eight male Wistar rats were divided into 4 groups of control, gentamicin (100 mg/kg), and gentamicin plus 50- and 100-mg/kg/day fucoidan pretreatment. In the end, all rats were killed, and then urine, blood, and tissue samples were prepared. Kidney weight (KW), body weight (BW), and 24-hour urine volume, as well as serum creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity, were measured. Kidney samples were also evaluated for histopathological changes. Results: Gentamicin significantly increased KW, KW/BW ratio, 24-hour urine volume, serum Cr, MDA, and BUN levels; however, fucoidan pretreatment, especially at a dose of 50 mg/kg, significantly returned these variables near to the control group values. Gentamicin also decreased BW gain, Cr clearance, SOD activity, and the degree of renal tissue damage compared to the control group, while treatment with fucoidan significantly reversed these alterations. Conclusions: The results show that fucoidan from S. angustifolium C. Agardh 1820 ameliorates gentamicin-induced nephrotoxicity by alleviating oxidative stress and augmenting antioxidant enzymes activity in renal tissue, suggesting the potential use of this fucoidan in a clinical setting.

Protective effect of chondroitin sulfate nano-selenium on chondrocyte of patients with Kashin-Beck disease

2021 ◽  
pp. 088532822098842
Author(s):  
Lichun Qiao ◽  
Abebe F Amhare ◽  
Huan Deng ◽  
Yizhen Lv ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Protective Effect ◽  
Chondroitin Sulfate ◽  
Mrna Level ◽  
Ultrastructural Changes ◽  
Control Group ◽  
Mitochondrial Morphology ◽  
Caspase 9 ◽  
Supplement Group ◽  
Cyt C ◽  
Beck Disease

Objective To investigate the protective effect of chondroitin sulfate nano-selenium (SeCS) on chondrocyte of Kashin-Beck disease (KBD). Methods Chondrocyte samples were isolated from the cartilage of three male KBD patients (54–57 years old). The chondrocytes were respectively divided into four groups: (a) control group, (b) SeCS supplement group (100 ng/mL SeCS), (c) T-2 + SeCS supplement group (20 ng/mL T-2 + 100 ng/mL SeCS), and (d) T-2 group (20 ng/mL T-2). Live/dead staining and transmission electron microscopy (TEM) were used to observe cell viability and ultrastructural changes in chondrocytes respectively. Expressions of Caspase-9, cytochrome C (Cyt-C), and chondroitin sulfate (CS) structure-modifying sulfotransferases including carbohydrate sulfotransferase 3, 15 (CHST-3, CHST-15), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction. Results After one- or three-days intervention, the number of living chondrocytes in the SeCS supplement group was higher than that in the control group, while it is opposite in the T-2 + SeCS supplement group and T-2 group. The cellular villi number in the surface increased in the SeCS supplement group compared with the control group. Mitochondrial morphology density was improved in the T-2 + SeCS supplement group compared with the T-2 group. Expressions of CHST-3, CHST-15, UST, Caspase-9, and Cyt-C on the mRNA level significantly increased in the T-2 + SeCS supplement group and T-2 group compared with the control group. Conclusions SeCS supplement increased the number of living chondrocytes, improved the ultrastructure, and altered the expressions of CS structure-modifying sulfotransferases, Caspase-9, and Cyt-C.

scholarly journals Effect of allopurinol on diabetic nephropathy; a double-blind clinical trial study

2020 ◽  
Vol 10 (1) ◽  
pp. e03-e03
Author(s):  
Saeed Mardani ◽  
Farzaneh Kadkhodaei-Elyaderani ◽  
Ali Momeni ◽  
Maryam Saeedi
Keyword(s):  
Clinical Trial ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Urinary Protein ◽  
Control Group ◽  
Double Blind ◽  
Diabetic Kidney ◽  
Lymphocyte Ratio ◽  
Double Blind Clinical Trial

Introduction: Diabetic nephropathy (diabetic kidney disease) is the most common cause of renal failure. Objectives: Regarding the role of allopurinol in the improvement of diabetic kidney disease, this study aimed to investigate the ameliorative effect of allopurinol in diabetic nephropathy patients. Patients and Methods: This double-blind clinical trial study was performed on 60 patients with diabetic kidney disease referenced to nephrology clinic during 2019-2020. Patients were divided into case (treated with allopurinol 100 mg/d) and control (received placebo pill) groups. Three and six months of intervention, complete blood count (CBC), fasting blood sugar levels (FBS), serum blood urea nitrogen (BUN) levels, creatinine (Cr) and uric acid (UA) levels, 24 hours urinary protein, glomerular filtration rate (GFR), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were measured and compared between the two groups. Results: After six months, reduction of UA and 24 hours urinary protein were not significant in the control group (P > 0.05) but it was significant in the allopurinol group (P < 0.05). In the allopurinol group, NLR and PLR levels decreased significantly during the six months (P < 0.01) however there was no significant change in the control group (P > 0.05). Conclusion: Low dosage of allopurinol (100 mg/d) reduces UA, proteinuria, NLR and PLR in patients after six months. Therefore it can be used for diabetic nephropathy patients as a supplementary, inexpensive and safe treatment.

scholarly journals Effect of N-acetylcysteine on pulmonary cell death in a controlled hemorrhagic shock model in rats

2012 ◽  
Vol 27 (8) ◽  
pp. 561-565 ◽  
Author(s):  
Paulo Fernandes Saad ◽  
Karen Ruggeri Saad ◽  
Luiz Dantas de Oliveira Filho ◽  
Sueli Gomes Ferreira ◽  
Marcia Kiyomi Koike ◽  
...  
Keyword(s):  
Cell Death ◽  
Hemorrhagic Shock ◽  
Fluid Resuscitation ◽  
Caspase 3 ◽  
Control Group ◽  
Albino Rats ◽  
Shock Model ◽  
Tissue Samples ◽  
Ringer’S Lactate ◽  
Hemorrhagic Shock Model

PURPOSE: To evaluate the effect of N-acetylcysteine (NAC) combined with fluid resuscitation on pulmonary cell death in rats induced with controlled hemorrhagic shock (HS). METHODS: Two arteries (MAP calculation and exsanguination) and one vein (treatments) were catheterized in 22 anesthetized rats. Two groups of male albino rats were induced with controlled HS at 35mmHg MAP for 60 min. After this period, the RL group was resuscitated with Ringer's lactate and the RL+NAC group was resuscitated with Ringer's lactate combined with 150mg/Kg NAC. The control group animals were cannulated only. The animals were euthanized after 120 min of fluid resuscitation. Lung tissue samples were collected to evaluate the following: histopathology, TUNEL and imunohistochemical expression of caspase 3. RESULTS: RL showed a greater number of cells stained by TUNEL than RL + NAC, but there was no change in caspase 3 expression in any group. CONCLUSION: N-acetylcysteine associate to fluid resuscitation, after hemorrhagic shock, decreased cell death attenuating lung injury.

scholarly journals The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate‐induced rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Farhad Koohpeyma ◽  
Morvarid Siri ◽  
Shaghayegh Allahyari ◽  
Marzieh Mahmoodi ◽  
Forough Saki ◽  
...  
Keyword(s):  
Uric Acid ◽  
Group Treatment ◽  
Monosodium Glutamate ◽  
Renal Tissue ◽  
Male Rats ◽  
Control Group ◽  
Protective Effects ◽  
Cell Protection ◽  
Caspase 9 ◽  
Genes Expression

Abstract Background Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible damages induced by MSG effects on some organs have been stated in experimental animal models. The aim of the present study was to evaluate the protective effects of L-carnitine (L-ca) on the renal tissue in MSG-Induced Rats. Methods In this regard, 60 male rats were randomly divided into six groups (n = 10/each): 1 (Control); 2 (sham); 3 (L-carnitine 200 mg/kg b.w); 4 (MSG 3 g/kg b.w); 5 (MSG + L-carnitine 100 mg/kg); and 6 (MSG + L-carnitine 200 mg/kg). After 6 months, the rats were sacrificed, the blood sample collected and the kidneys harvested for evaluation of biochemical analytes, genes expression, and histopathological changes. Results MSG significantly increased the serum level of MDA, BUN, creatinine, uric acid and renal Caspase-9, NGAL and KIM-1 expression, but it decreased the serum activity also renal expression of SOD, catalase, GPX, and Bcl-2 expression compared to the control group. Treatment with L-ca significantly reduced the serum BUN, creatinine, uric acid and MDA level and increased catalase, GPX and SOD compared to the MSG group. However, only administration of L-ca 200 significantly decreased the caspase-9, NGAL and KIM-1; also, it increased the Bcl-2 expression in the kidney compared to the MSG group. Conclusions Our findings indicated that L-carnitine had a major impact on the cell protection and might be an effective therapy in ameliorating the complications of the kidney induced by MSG via its antioxidant and anti-apoptotic properties.

scholarly journals Hu-Lu-Ba-Wan Attenuates Diabetic Nephropathy in Type 2 Diabetic Rats through PKC-α/NADPH Oxidase Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lishan Zhou ◽  
Hui Dong ◽  
Yi Huang ◽  
Lijun Xu ◽  
Xin Zou ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nadph Oxidase ◽  
Signaling Pathway ◽  
Superoxide Anion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Control Group ◽  
Type 2 Diabetic

Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-α) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-αin renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.

scholarly journals Effect of spironolactone on diabetic nephropathy in albino rats: ultrastructural and immunohistochemical study

2017 ◽  
Vol 3 (5) ◽  
pp. 110
Author(s):  
Hassan M. Rezk ◽  
Mohamed El-Sherbiny ◽  
Hoda Atef ◽  
Medhat Taha ◽  
Samar Hamdy ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Interstitial Fibrosis ◽  
Diabetic Rats ◽  
Ultrastructural Changes ◽  
Control Group ◽  
Albino Rats ◽  
Electron Microscopic ◽  
Group V ◽  
Group I

<p class="abstract"><strong>Background:</strong> Diabetic nephropathy (DN) has become one of the most common causes of end stage renal disease (ESRD). Hyperglycemia induces oxidative stress in renal tubular epithelial cells that initiate tubulointerstitial fibrosis, which is a characteristic feature of diabetic nephropathy that becomes progressively complicated by renal failure. Aim: To assess the effect of spironolactone (SPL) on WT-1 protein expression and ultrastructural changes associated with the progression of experimental diabetic nephropathy (DN).</p><p class="abstract"><strong>Methods:</strong> Forty female albino rats were divided into five groups. Group I (control group), Group II (untreated diabetic rats), Group III (insulin-treated diabetic rats), Group IV (spironolactone-treated diabetic rats) and Group V (insulin and spironolactone-treated diabetic rats). At the 4<sup>th</sup> and 8<sup>th</sup> weeks, 4 rats from each group were sacrificed and renal tissue and blood samples were obtained. The rats were anaesthetized using ether inhalation. Each kidney was longitudinally divided and processed for immunohistochemical analysis with rabbit polyclonal anti-WT-1 Antibody and electron microscopic examination.</p><p class="abstract"><strong>Results:</strong> Treatment of STZ-induced diabetic rats with insulin and spironolactone (Group V) showed improvement in renal corpuscles as well as their capsular space, the basement membrane became normal with preserved minor and major processes and subpodocytic space, most of the proximal convoluted tubules retained their brush border, and their cells showed normal euchromatic nuclei and scattered mitochondria with apical microvilli, which is similar to the findings of the control group. Quantitative analyses showed significant increase in area of fibrosis and focal thickening of the glomerular basement membrane in non-SPL treated groups. There was a marked decrease in proteinuria compared to other treated groups. The results were better after 8 weeks compared to those after 4 weeks.</p><strong>Conclusions:</strong> The administration of SPL significantly prevented the extent of interstitial fibrosis in the diabetic kidney.

Hepatocyte ultrastructural alterations in perimetastatic areas

1996 ◽  
Vol 54 ◽  
pp. 768-769
Author(s):  
H. J. Finol ◽  
M. E. Correa ◽  
L.A. Sosa ◽  
A. Márquez ◽  
N.L. Díaz
Keyword(s):  
Malignant Tumor ◽  
Malignant Tumors ◽  
Surrounding Tissue ◽  
Ultrastructural Changes ◽  
Pancreas Carcinoma ◽  
Duct Carcinoma ◽  
Tissue Samples ◽  
Primary Malignant Tumor ◽  
Transmission Electron ◽  
Remote Sites

In classical oncological literature two mechanisms for tissue aggression in patients with cancer have been described. The first is the progressive invasion, infiltration and destruction of tissues surrounding primary malignant tumor or their metastases; the other includes alterations produced in remote sites that are not directly affected by any focus of disease, the so called paraneoplastic phenomenon. The non-invaded tissue which surrounds a primary malignant tumor or its metastases has been usually considered a normal tissue . In this work we describe the ultrastructural changes observed in hepatocytes located next to metastases from diverse malignant tumors.Hepatic biopsies were obtained surgically in patients with different malignant tumors which metatastized in liver. Biopsies included tumor mass, the zone of macroscopic contact between the tumor and the surrounding tissue, and the tissue adjacent to the tumor but outside the macroscopic area of infiltration. The patients (n = 5), 36–75 years old, presented different tumors including rhabdomyosarcoma, leiomyosarcoma, pancreas carcinoma, biliar duct carcinoma and colon carcinoma. Tissue samples were processed with routine techniques for transmission electron microscopy and observed in a Hitachi H-500 electron microscope.

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