Aristolochic acid I as an emerging biogenic contaminant involved in chronic kidney diseases: A comprehensive review on exposure pathways, environmental health issues and future challenges.

Described in the 1950s, Balkan Endemic Nephropathy (BEN) has been recognized as a chronic kidney disease (CKD) with clinical peculiarities and multiple etiological factors. Environmental contaminants - aromatic compounds, mycotoxins and phytotoxins like aristolochic acids (AAs) - polluting food and drinking water sources, were incriminated in BEN, due to their nephrotoxic and carcinogenic properties. The implication of AAs in BEN etiology is currently a highly debated topic due to the fact that they are found within the Aristolochiaceae plants family, used around the globe as traditional medicine and they were also incriminated in Aristolochic Acid Nephropathy (AAN). Exposure pathways have been investigated, but it is unclear to what extent AAs are acting alone or in synergy with other cofactors (environmental, genetics) in triggering kidney damage. Experimental studies strengthen the hypothesis that AAI, the most studied compound in the AAs class, is a significant environmental contaminant and a most important causative factor of BEN. The aim of this review is to compile information about the natural exposure pathways to AAI, via traditional medicinal plants, soil, crop plants, water, food, air. Data that either supports or contradicts the AAI theory concerning BEN etiology was consolidated and available solutions to reduce human exposure were discussed. Because AAI is a phytotoxin with physicochemical properties that allow its transportation in environmental matrices from different types of areas (endemic, nonendemic), and induce CKDs (BEN, AAN) and urinary cancers through bioaccumulation, this review aims to shed a new light on this compound as a biogenic emerging pollutant.

Complexation of Danube common nase (Chondrostoma nasus L.) oil by ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin.

ß-Cyclodextrin- and 2-hydroxypropyl-ß-cyclodextrin/Danube common nase (Chondrostoma nasus L.) oil complexes (ß-CD- and HP-ß-CD/CNO) have been obtained for the first time. The fatty acid (FA) profile of the CNO indicates an important content of polyunsaturated fatty acids, the most important being eicosapentaenoic acid (EPA, 6.3%) and docosahexaenoic acid (DHA, 1.6%), both ω-3 FAs. The complexes have been obtained by kneading method. The moisture content and successful of molecular encapsulation have been evaluated by thermal and spectroscopic techniques. Thermogravimetry and differential scanning calorimetry analyses reveals that the moisture content of CD/CNO complexes significantly decreased, compared to starting CDs. On the other hand, the crystallinity index was for the first time determined for such type of complexes, the ß-CD/CNO complex having values of 43.9(±18.3)%, according to X-ray diffractometry. FA profile and CD/CNO characteristics sustain the use of these ω-3 based complexes for food supplements or functional food products, but further studies are needed.

Balkan endemic nephropathy and aristolochic acid I: an investigation into the role of soil and soil organic matter contamination, as a potential natural exposure pathway.

Aristolochic acids (AAs) are carcinogenic and nephrotoxic plant alkaloids present in Aristolochia species, used in traditional medicine. Recent biomolecular and environmental studies have incriminated these toxins as an etiological agent in Balkan endemic nephropathy (BEN), a severe kidney disease occurring in the Balkan Peninsula. The questions on how the susceptible populations are exposed to these toxins have not yet been clearly answered. Exposure to AAs through the food chain, and environmental pollution (soil/dust), could provide an explanation for the presence of BEN in the countries where no folkloric use of the plant has been documented (Bulgaria, Croatia). Additional exposure pathways are likely to occur, and we have shown previously that AAs can contaminate crop plants through absorption from soil, under controlled laboratory environment. Here, we attempt to provide additional support to this potential exposure pathway, by revealing the presence of AAI in soil and soil organic matter samples collected from BEN and non-BEN areas. The samples were processed in order to be analyzed by high-pressure liquid chromatography, and ion trap mass spectrometry. Our results showed the presence of AAI in small concentrations, both in BEN and non-BEN soils, especially where Aristolochia plants and seeds were present.

Thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) and complexation with ß-cyclodextrin.

The thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) as well as its ß-cyclodextrin (ß-CD) complexation ability has been verified for the first time. The main omega-3 fatty acids, EPA and DHA, were significantly degraded, even at 50 °C. Their relative concentrations decrease from 6.1% for EPA and 4.1% for DHA to 1.7% and 1.5% after degradation at 150 °C, respectively. On the other hand, the relative concentrations of monounsaturated and saturated fatty acids remained constant or slightly increased by a few percent after degradation (e.g., from 10.7% to 12.9% for palmitic acid). Co-crystallization of ASO with ß-CD at a host-guest ratio of 1:1 and 3:1 from an ethanol-water mixture and kneading methods has been used for the preparation of ß-CD/ASO complexes. The analysis of the complexes by thermogravimetry, differential scanning calorimetry (DSC), and Karl Fischer titration (KFT) as well as the decrease of the "strongly-retained" water content confirm the formation of the inclusion compound. Furthermore, the DSC parameters correlate well with the KFT kinetic data for ß-CD/ASO complexes.

Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets.

Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc.

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/ß-cyclodextrin supramolecular system.

Ocimum basilicum L. essential oil and its ß-cyclodextrin (ß-CD) complex have been investigated with respect to their stability against the degradative action of air/oxygen and temperature. This supramolecular system was obtained by a crystallization method in order to achieve the equilibrium of complexed-uncomplexed volatile compounds in an ethanol/water solution at 50 °C. Both the raw essential oil and its ß-CD complex have been subjected to thermal and oxidative degradation conditions in order to evaluate the protective capacity of ß-CD. The relative concentration of the O. basilicum L. essential oil compounds, as determined by GC-MS, varies accordingly with their sensitivity to the thermal and/or oxidative degradation conditions imposed. Furthermore, the relative concentration of the volatile O. basilicum L. compounds found in the ß-CD complex is quite different in comparison with the raw material. An increase of the relative concentration of linalool oxide from 0.3% to 1.1%, in addition to many sesquiterpene oxides, has been observed. ß-CD complexation of the O. basilicum essential oil modifies the relative concentration of the encapsulated volatile compounds. Thus, linalool was better encapsulated in ß-CD, while methylchavicol (estragole) was encapsulated in ß-CD at a concentration close to that of the raw essential oil. Higher relative concentrations from the degradation of the oxygenated compounds such as linalool oxide and aromadendren oxide were determined in the raw O. basilicum L. essential oil in comparison with the corresponding ß-CD complex. For the first time, the protective capability of natural ß-CD for labile basil essential oil compounds has been demonstrated.

Arachidonic acid accumulates in the stromal macrophages during thymus involution in diabetes.

Diabetes is a debilitating disease with chronic evolution that affects many tissues and organs over its course. Thymus is an organ that is affected early after the onset of diabetes, gradually involuting until it loses most of its thymocyte populations. We show evidence of accumulating free fatty acids with generation of eicosanoids in the diabetic thymus and we present a possible mechanism for the involution of the organ during the disease. Young rats were injected with streptozotocin and their thymuses examined for cell death by flow cytometry and TUNEL reaction. Accumulation of lipids in the diabetic thymus was investigated by histology and electron microscopy. The identity and quantitation of accumulating lipids was done with gas chromatography-mass spectrometry and liquid chromatography. The expression and dynamics of the enzymes were monitored via immunohistochemistry. Diabetes causes thymus involution by elevating the thymocyte apoptosis. Exposure of thymocytes to elevated concentration of glucose causes apoptosis. After the onset of diabetes, there is a gradual accumulation of free fatty acids in the stromal macrophages including arachidonic acid, the substrate for eicosanoids. The eicosanoids do not cause thymocyte apoptosis but administration of a cyclooxygenase inhibitor reduces the staining for ED1, a macrophage marker whose intensity correlates with phagocytic activity. Diabetes causes thymus involution that is accompanied by accumulation of free fatty acids in the thymic macrophages. Excess glucose is able to induce thymocyte apoptosis but eicosanoids are involved in the chemoattraction of macrophage to remove the dead thymocytes.

Tumour-associated fibroblasts and mesenchymal stem cells: more similarities than differences.

Tumour-associated fibroblasts (TAFs) are part of the tumour stroma, providing functional and structural support for tumour progression and development. The origin and biology of TAFs are poorly understood, but within the tumour environment, TAFs become activated and secrete different paracrine and autocrine factors involved in tumorigenesis. It has been shown that bone marrow mesenchymal stem cells (MSCs) can be recruited into the tumours, where they proliferate and acquire a TAF-like phenotype. We attempted to determine to what extent TAFs characteristics in vitro juxtapose to MSCs' definition, and we showed that TAFs and MSCs share immunophenotypic similarities, including the presence of certain cell surface molecules [human leukocyte antigen-DR subregion (HLA-DR), CD29, CD44, CD73, CD90, CD106 and CD117]; the expression of cytoskeleton and extracellular matrix proteins, such as vimentin, α-smooth muscle actin, nestin and trilineage differentiation potential (to adipocytes, chondrocytes and osteoblasts). When compared to MSCs, production of cytokines, chemokines and growth factors showed a significant increase in TAFs for vascular endothelial growth factor, transforming growth factor-ß1, interleukins (IL-4, IL-10) and tumour necrosis factor α. Proliferation rate was highly increased in TAFs and fibroblast cell lines used in our study, compared to MSCs, whereas ultrastructural details differentiated the two cell types by the presence of cytoplasmic elongations, lamellar content lysosomes and intermediate filaments. Our results provide supportive evidence to the fact that TAFs derive from MSCs and could be a subset of 'specialized' MSCs.