scholarly journals Are statins toxic or safe for kidney diseases? An updated mini-review study

2020 ◽  
Vol 9 (4) ◽  
pp. e38-e38
Author(s):  
Shadi Botshekan ◽  
Banafsheh Yalameha

Statins, as the most important cholesterol-lowering agents, inhibit the production of blood cholesterol by blocking an enzyme called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase. Statins have beneficial effects in some tissues during various injuries. Recent evidence suggests that unlike the beneficial effects of statins, administration of high doses of these drugs may increase renal impairment, although more research is needed in this regard. Therefore, this study aimed to evaluate the possible effect of different doses of statins on the morphology and function of the kidney tubular cells.

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 239-250 ◽  
Author(s):  
Gérard Alonso ◽  
Evelyne Galibert ◽  
Véra Boulay ◽  
Anne Guillou ◽  
Alexandra Jean ◽  
...  

The hypothalamic hormone vasopressin (AVP) has known mitogenic effects on various cell types. This study was designed to determine whether sustained elevated levels of circulating AVP could influence cell proliferation within adult tissues known to express different AVP receptors, including the pituitary, adrenal gland, liver, and kidney. Plasmatic AVP was chronically increased by submitting animals to prolonged hyperosmotic stimulation or implanting them with a AVP-containing osmotic minipump. After several days of either treatment, increased cell proliferation was detected only within the kidney. This kidney cell proliferation was not affected by the administration of selective V1a or V1b receptor antagonists but was either inhibited or mimicked by the administration of a selective V2 receptor antagonist or agonist, respectively. Kidney proliferative cells mostly concerned a subpopulation of differentiated tubular cells known to express the V2 receptors and were associated with the phosphorylation of ERK. These data indicate that in the adult rat, sustained elevated levels of circulating AVP stimulates the proliferation of a subpopulation of kidney tubular cells expressing the V2 receptor, providing the first illustration of a mitogenic effect of AVP via the activation of the V2 receptor subtype. Elevated levels of circulating vasopressin selectively stimulate the proliferation of kidney tubular cells via the activation of V2 receptors, thus showing the potential implication in polycystic kidney diseases.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kwon Moo Park ◽  
Min Jung Kong

Abstract Background and Aims The primary cilia play a key role in the maintenance of cell homeostasis by sensing and transducing extracellular signals into the cell and are associated with several kidney diseases including ADPKD. Here, we investigated whether water restriction affects the length of primary cilia of kidney tubule cells and its underlying mechanisms. Method Some mice were not supplied with water for 2 days and then the length of primary cilia were determined by immunostaining using acetylated-α-tubulin (ac-α-tubulin) antibody. Madin-Darby canine kidney (MDCK) cells were exposed to high concentration of NaCl or mannitol and the lengths of primary cilia were determined under microscope. Results Water restriction shortened primary cilia length in kidney tubular cells along with the increase of urine osmolality. Water restriction lowered the expression of acetylated-α-tubulin (ac-α-tubulin), EXOC5, one of the components of exocyst complex, and α-tubulin transferase in the kidney. In MDCK cells, high concentration of NaCl or mannitol treatments shortened primary cilia length and decreased the expression of ac-α-tubulin, EXOC5, and α-tubulin transferase. Conclusion These findings demonstrate that water restriction induces the shortening of primary ciliua in kidney tubule cells along with increased urine osmolality, suggesting that primary cilia are involved in the urine concentric process.


2018 ◽  
Vol 25 (27) ◽  
pp. 3256-3271 ◽  
Author(s):  
Shikun Yang ◽  
Aimei Li ◽  
JianWen Wang ◽  
Jun Liu ◽  
Yachun Han ◽  
...  

Background: Kidney disease is a serious problem that adversely affects human health, but critical knowledge is lacking on how to effectively treat established chronic kidney disease. Mounting evidence from animal and clinical studies has suggested that Vitamin D Receptor (VDR) activation has beneficial effects on various renal diseases. Methods: A structured search of published research literature regarding VDR structure and function, VDR in various renal diseases (e.g., IgA nephropathy, idiopathic nephrotic syndrome, renal cell carcinoma, diabetic nephropathy, lupus nephritis) and therapies targeting VDR was performed for several databases. Result: Included in this study are the results from 177 published research articles. Evidence from these papers indicates that VDR activation is involved in the protection against renal injury in kidney diseases by a variety of mechanisms, including suppression of RAS activation, anti-inflammation, inhibiting renal fibrogenesis, restoring mitochondrial function, suppression of autoimmunity and renal cell apoptosis. Conclusion: VDR offers an attractive druggable target for renal diseases. Increasing our understanding of VDR in the kidney is a fertile area of research and may provide effective weapons in the fight against kidney diseases.


1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.


2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.


Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2715
Author(s):  
Rodica Ana Ungur ◽  
Viorela Mihaela Ciortea ◽  
Laszlo Irsay ◽  
Alina Deniza Ciubean ◽  
Bogdana Adriana Năsui ◽  
...  

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in knee OA (osteoarthritis) treatment. Despite their efficiency in pain and inflammation alleviation, NSAIDs accumulate in the environment as chemical pollutants and have numerous genetic, morphologic, and functional negative effects on plants and animals. Ultrasound (US) therapy can improve pain, inflammation, and function in knee OA, without impact on environment, and with supplementary metabolic beneficial effects on cartilage compared to NSAIDs. These features recommend US therapy as alternative for NSAIDs use in knee OA treatment.


Author(s):  
Yiping Hu ◽  
Juan He ◽  
Lianhua He ◽  
Bihua Xu ◽  
Qingwen Wang

AbstractTransforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.


2021 ◽  
Vol 14 (6) ◽  
pp. 593
Author(s):  
Sandra Fernández-Rodríguez ◽  
Claudia Esposito-Zapero ◽  
Teodoro Zornoza ◽  
Ana Polache ◽  
Luis Granero ◽  
...  

N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper, we set out to assess both the potential involvement of the glutamate metabotropic receptors (mGluR) in the possible dual effect of NAC administered at two different doses and NAC’s effect on ethanol-induced activation. To this aim, 30 or 120 mg/kg of NAC was intraperitoneally administered to rats with the presence or absence of the negative allosteric modulator of mGluR5 (MTEP 0.1 mg/kg). Thereafter, the cFOS IR-cell expression was analyzed. Secondly, we explored the effect of 120 mg/kg of NAC on the neurochemical and behavioral activation induced by intra-VTA ethanol administration (150 nmol). Our results showed that the high NAC dose stimulated cFOS expression in the NAcc, and that this effect was suppressed in the presence of MTEP, thus suggesting the implication of mGluR5. Additionally, high doses could attenuate the ethanol-induced increase in cFOS-expression in the NAcc, probably due to a phenomenon based on the long-term depression of the MSNs. Additional experiments are required to corroborate our hypothesis.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.


2021 ◽  
Vol 9 (3) ◽  
pp. 547
Author(s):  
Daniel Sánchez ◽  
Iva Hoffmanová ◽  
Adéla Szczepanková ◽  
Věra Hábová ◽  
Helena Tlaskalová-Hogenová

The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.


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