Amelioration of diabetic nephropathy using pomegranate peel extract-stabilized gold nanoparticles: assessment of NF-κB and Nrf2 signaling system.

BACKGROUND: Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer. PURPOSE: This study was designed to investigate the ameliorative role of pomegranate peel extract-stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model. METHODS: Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence. RESULTS: The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic ß-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZ-induced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis. CONCLUSION: The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN.

Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management.

BACKGROUND: Henoch-Schönlein purpura (HSP) is one of the most common vasculitides in children. It is manifested by skin purpura, arthritis, abdominal pain, renal involvement, etc. Typically, HSP is considered to be self-limiting, although renal involvement (HSP purpura nephritis, HSPN) is the principal cause of morbidity from this disease. For this reason, it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for HSPN. In this article, we review the updated pathophysiology and treatment strategies for HSPN. DATA SOURCES: We searched databases including PubMed, Elsevier and Wanfang for the following key words: Henoch-Schönlein purpura, nephritis, mechanism and treatment, and we selected those publications written in English that we judged to be relevant to the topic of this review. RESULTS: Based on the data present in the literature, we reviewed the following topics: 1) the possible pathogenesis of HSPN: several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury; 2) multiple-drug treatment for HSPN: although there have been few evidence-based treatment strategies for HSPN, several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological severity. CONCLUSIONS: HSPN is a severe disease of childhood. To better understand this disease, detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.

Serial non-invasive assessment of antibody induced nephritis in mice using positron emission tomography.

Mouse models of experimental anti-glomerular basement membrane (anti-GBM) nephritis provide an analytical tool for studying spontaneous lupus nephritis. The potential of Positron Emission Tomography (PET) was evaluated using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) as a probe to monitor the progression of anti-GBM induced nephritis in a mouse model. The imaging results were compared to conventional measures of renal function and pathological changes. Serum and urinary vascular cell adhesion molecule-1 (VCAM-1) levels were used as measures of endothelial cell activation and inflammation. Following a challenge with anti-glomerular antibodies, mice exhibited peak changes in serum creatinine, proteinuria, and glomerulonephritis score at 14 days post-challenge (p.c.). In contrast, VCAM levels peaked at day 7 p.c. On dynamic PET images (0-60 min) of day 7, kidneys of the anti-GBM nephritis mice demonstrated a unique pattern of FDG uptake. Compared to the time activity curve (TAC) prior to challenge, a rightward shift was observed after the challenge. By day 10 p.c., kidney FDG uptake was lower than baseline and remained so until the study ended at 21 days p.c. During this time frame measures of renal dysfunction remained high but VCAM-1 levels declined. These changes were accompanied by an increase in kidney volume as measured by Computed Tomography (CT) and intra-abdominal fluid collection. Our results suggest that FDG-PET-CT can be used as a non-invasive imaging tool to longitudinally monitor the progression of renal disease activity in antibody mediated nephritis and the magnitude of renal FDG retention correlates better with early markers of renal inflammation than renal dysfunction.

An assessment of the tumorigenic properties of a Hudson County soil sample heavily contaminated with hexavalent chromium.

During much of this century, Hudson County, New Jersey, was a major center for the processing of chromium ore. Some of the residue from this processing was used in landfills and in construction materials throughout the county and, in some cases, in highly populated areas. Given that it is widely accepted that exposure to hexavalent chromium compounds poses a risk for the development of respiratory-tract cancer, concerns were raised that individuals who worked or resided in chromium-contaminated areas might be at increased risk for the development of respiratory cancer. To address these concerns, we evaluated a Hudson County soil sample-heavily contaminated with chromium ore residue (Cr(+6) concentration at 5 895 mg/kg)-with respect to its carcinogenic potential to the respiratory tract of Sprague-Dawley rats. Groups of animals were given repeated intratracheal exposures to one of four materials: (1) Hudson County chromium-contaminated soil (CCS), (2) CCS augmented with calcium chromate (CaCrO4), (3) CaCrO4 alone, or (4) control soil. Nominal total doses of Cr(+6) for each respective group were 324 microg/kg, 7,975 microg/kg, 8,700 microg/kg, and 0.02 microg/kg. Incidences of malignant tumors and nephritis were not elevated in any group. Four primary lung tumors appeared in animals that received CCS + CaCrO4, and one primary lung tumor appeared in the group treated with CaCrO4 alone. These incidences were not significant statistically, but the rare spontaneous occurrence of these tumors in Sprague-Dawley rats suggested that they were treatment related. No primary lung tumors appeared in the control or CCS-treated groups.

[The catamnestic assessment of the efficacy of combined pathogenetic therapy in patients with different clinico-morphological variants of chronic glomerulonephritis]. / Katamnesticheskaia otsenka éffektivnosti kompleksnoi patogeneticheskoi terapii bol'nykh s razlichnymi kliniko-morfologicheskimi variantami khronicheskogo glomerulonefrita.

In 70 patients with functionally compensated chronic glomerulonephritis (CGN), the disease outcomes were elucidated after the use of the 4-component therapy (a cytostatic, an anticoagulant, an antiaggregation agent and prednisone). The therapy appeared much more effective in the nephrotic types of CGN than in the active nephritic types. Remission was only attained in a subgroup of patients with the active types: with an early stage of the maximally active type of mesangiocapillary CGN. In the nephrotic type CGN, the therapy was effective in short-phase disease and ineffective in long persistence of that syndrome. In the nephrotic types, mesangioproliferative CGN as well as the short-phase nephrotic syndrome irrespective of the morphological type turned out predictors of a favourable outcome following the treatment. No effect can be predicted in focal segmental hyalinosis/sclerosis accompanied by arterial hypertension and the protracted nephrotic syndrome.