benzofurans and Kidney-Diseases

Benzbromarone1 is a benzofuran derivative which lowers serum urate and increases urinary urate excretion in normal, hyperuricaemic and gouty subjects. In open short- and long-term studies benzbromarone reduced serum uric acid levels by one-third to one-half and maintained its effectiveness for periods of up to 8 years. Single-dose experimental studies have shown benzbromarone to have a urate-lowering effect similar to that of a therapeutic dose of probenecid or sulphinpyrazone, but unlike these drugs benzbromarone can be administered in a once daily regimen. In 2 short-term comparative therapeutic trials in a small number of patients with hyperuricaemia, 80mg of micronised benzbromarone daily was at least as effective as 1000mg of probenecid or 300mg of allopurinol daily in lowering serum uric acid levels. Side-effects during benzbromarone administration are usually mild and primarily gastrointestinal in nature.

Topics: Aspirin; Benzbromarone; Benzofurans; Drug Interactions; Fasting; Gout; Humans; Kidney Diseases; Kinetics; Lipid Metabolism; Pyrazinamide; Triglycerides; Uric Acid; Xanthine Oxidase

Approximately one-third of patients with type 2 diabetes mellitus (T2DM) have concurrent renal impairment. There are limited therapeutic options for these patients. Fasiglifam is a G protein-coupled receptor 40 agonist that was under investigation for the treatment of T2DM. The objective of this study was to evaluate the potential effect of renal impairment on the pharmacokinetics and safety of a single dose of fasiglifam and its metabolite M-1.. This was a phase I, open-label, parallel-group study. Subjects with varying degrees of renal function received a single oral dose of fasiglifam 50 mg. Blood and urine samples were collected through 168 h postdose. Study endpoints were pharmacokinetic and safety variables.. Fifty-three subjects were enrolled. Mean fasiglifam plasma concentrations were higher in subjects with mild renal impairment compared with other groups, but within each renal function cohort, plasma concentrations tended to decrease with decreasing renal function. Regression analyses indicated that fasiglifam exposure decreased and M-1 exposure increased with decreasing renal function. Predicted exposure values at about the midpoint of creatinine clearance for each renal impairment group differed by up to 21% (fasiglifam) and 87% (M-1) from that of the normal renal function group. Hemodialysis had no effect on fasiglifam or M-1 exposure. Fasiglifam renal clearance (CLR) was not affected, but M-1 CLR decreased with increasing impairment. No incidences of hypoglycemia were reported during the study.. Varying renal function status did not have a significant impact on the clearance of fasiglifam in this study.

Topics: Adult; Aged; Benzofurans; Female; Humans; Hypoglycemic Agents; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Sulfones

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Benzofurans; Clinical Trials as Topic; Gout; Humans; Kidney Diseases; Kidney Failure, Chronic; Metabolic Clearance Rate; Middle Aged; Urea; Uric Acid

Topics: Aspirin; Benzofurans; Chlorothiazide; Clinical Trials as Topic; Colchicine; Drug Combinations; Humans; Ketones; Kidney Diseases; Metabolic Diseases; Uric Acid

Salvianolic acid B (SAB) can alleviate renal fibrosis and improve the renal function.. To investigate the effect of SAB on renal tubulointerstitial fibrosis and explore its underlying mechanisms.. Male C57 mice were subjected to unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) for renal fibrosis indication. Vehicle or SAB (10 mg/kg/d, i.p.) were given consecutively for 2 weeks in UUO mice while 4 weeks in AAN mice. The serum creatinine (Scr) and blood urine nitrogen (BUN) were measured. Masson's trichrome staining and the fibrotic markers (FN and α-SMA) were used to evaluate renal fibrosis. NRK-49F cells exposed to 2.5 ng/mL TGF-β were treated with SAB in the presence or absence of 20 μM 3-DZNep, an inhibitor of EZH2. The protein expression of EZH2, H3k27me3 and PTEN/Akt signaling pathway in renal tissue and NRK-49F cells were measured by Western blots.. SAB significantly improved the levels of Scr by 24.3% and BUN by 35.7% in AAN mice. SAB reduced renal interstitial collagen deposition by 34.7% in UUO mice and 72.8% in AAN mice. Both. SAB might have therapeutic potential on renal fibrosis of CKD through inhibiting EZH2, which encourages further clinical trials.

Topics: Animals; Benzofurans; Depsides; Enhancer of Zeste Homolog 2 Protein; Fibrosis; Histones; Kidney; Kidney Diseases; Male; Mice; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Transforming Growth Factor beta1; Ureteral Obstruction

Ligusticum striatum DC. is traditionally used to treat ischemic diseases because of its potent effect against blood stasis and thrombosis, including various cardiovascular, cerebral and renal diseases. Senkyunolide I (SEI), which is the major active phthalide ingredient of Ligusticum striatum DC., is mainly distributed in kidney and has been shown to attenuate ischemia reperfusion injury in liver. However, the underlying effect of SEI against renal ischemia-reperfusion injury (IRI) remain unclear.. SEI protected renal function and structural integrity. It reversed the I/R-induced elevation of BUN, SCr levels and renal pathological injury. The secretion of proinflammatory cytokines including TNF-α and IL-6 was inhibited, and the renal apoptosis was attenuated by SEI. In addition, SEI played a protective role by reducing the production of reactive oxidative species (ROS), as shown by the elevated expression of antioxidant proteins including Nrf2, HO-1, NQO1, and reduced expression of endoplasmic reticulum stress (ERS) related proteins including GRP78 and CHOP. It also attenuated HK2 cell injury in an in vitro model induced by H. SEI alleviates renal injury induced by ischemia reperfusion with anti-inflammatory, anti-endoplasmic reticulum stress, anti-oxidative and anti-apoptotic effect.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Benzofurans; Blood Urea Nitrogen; Creatinine; Endoplasmic Reticulum Stress; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Reperfusion Injury

Renal interstitial fibrosis (RIF) is the main pathological feature of end-stage renal disease (ESRD) caused by various chronic kidney diseases (CKD), and is closely related to renal dysfunction and patient prognosis. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B), isolated from traditional Chinese medicine Salviae miltiorrhizae, have been confirmed to have anti-fibrotic effects on liver, cardiac and kidney. However, the precise molecular mechanism underlying the nephroprotective effects of Sal A and Sal B, and whether there is a difference between the two in RIF are still unclear.. This study investigated the pharmacological effects of Sal A and Sal B in RIF and explore the underlying mechanisms by in vivo and in vitro experiments.. The nephroprotective effects of Sal A, Sal B and Sal A+B were evaluated by assessing the parameters related to kidney function such as renal histology, renal function, urinary protein NAG, urinary β2 microglobulin. In addition, RIF-related markers such as CTCF and Par3 were also detected. Thereafter, the related protein or gene levels of PDGF-C/PDGFR-α signaling pathways, apoptosis and endoplasmic reticulum stress (ERS) were determined by western blot, real-time PCR, flow cytometry or immunofluorescence staining.. In vivo, the results showed that Sal A, Sal B and Sal A+B partially improved kidney dysfunction, increased the expression of Par-3 and reduced the expression of CTGF, PDGF-C and PDGFR-α. In vitro, the results also showed that Sal A, Sal B and Sal A+B reversed apoptosis and ERS in HSA-induced HK-2 cells via regulating PDGF-C/PDGFR-α signaling pathway.. This article revealed a novel mechanism linking PDGF-C/PDGFR-α signaling pathway to RIF and suggested that Sal A, Sal B and Sal A+B were considered as potential therapeutic agents for the amelioration of RIF.

Topics: Benzofurans; Caffeic Acids; Depsides; Fibrosis; Humans; Kidney Diseases; Lactates; Lymphokines; Platelet-Derived Growth Factor; Signal Transduction

Chronic Kidney Disease (CKD) is a serious threat to human health. In addition, kidney fibrosis is a key pathogenic intermediate for the progression of CDK. Moreover, excessive activation of fibroblasts is key to the development of kidney fibrosis and this process is difficult to control. Notably, fraxinellone is a natural compound isolated from Dictamnus dasycarpus and has a variety of pharmacological activities, including hepatoprotective, anti-inflammatory and anti-cancer effects. However, the effect of fraxinellone on kidney fibrosis is largely unknown. The present study showed that fraxinellone could alleviate folic acid-induced kidney fibrosis in mice in a dose dependent manner. Additionally, the results revealed that fraxinellone could effectively down-regulate the expression of CUGBP1, which was highly up-regulated in human and murine fibrotic renal tissues. Furthermore, expression of CUGBP1 was selectively induced by the Transforming Growth Factor-beta (TGF-β) through p38 and JNK signaling in kidney fibroblasts. On the other hand, downregulating the expression of CUGBP1 significantly inhibited the activation of kidney fibroblasts. In conclusion, these findings demonstrated that fraxinellone might be a new drug candidate and CUGBP1 could be a promising target for the treatment of kidney fibrosis.

Topics: Animals; Benzofurans; CELF1 Protein; Cell Line; Disease Models, Animal; Fibroblasts; Fibrosis; Folic Acid; JNK Mitogen-Activated Protein Kinases; Kidney; Kidney Diseases; Male; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Rats; Transforming Growth Factor beta1

Renal fibrosis is a kind of progressive kidney disease leading to end-stage renal damage. Epithelial-mesenchymal transition (EMT) is one of the crucial features of renal fibrosis. Salvianolic acid B (SalB), isolated from traditional Chinese medicine Radix Salviae miltiorrhizae, has been proved to be suitable for renal protection. The aims of this study are to investigate the pharmacological effects of SalB on renal fibrosis and explore the underlying mechanisms. In vivo, our study showed that SalB could improve kidney dysfunction and reduce the expression of EMT-related proteins, including fibronectin (FN), α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β). In addition, SalB activated autophagy and up-regulated the expression of Sirt1. In vitro, our study showed that SalB reversed EMT in TGF-β1-induced human kidney proximal tubular epithelial cells (HK-2 cells). Further mechanism studies showed that the inhibition of Sirt1 and autophagy could reverse the protective effect of SalB on the EMT process in TGF-β1-induced HK-2 cells. Taken together, this study demonstrated that SalB attenuates EMT in the process of renal fibrosis through activating Sirt1-mediated autophagy, and Sirt1 could be a key target for treatment of renal fibrosis.

Topics: Actins; Animals; Autophagy; Benzofurans; Cell Line; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibronectins; Fibrosis; Humans; Kidney; Kidney Diseases; Male; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1; Transforming Growth Factor beta

Following an acute insult, macrophages regulate renal fibrogenesis through the release of various factors that either encourage the synthesis of extracellular matrix synthesis or the degradation of matrix. To study Twist1 functions in different macrophage subsets during kidney scar formation, we used two conditional mutant mouse models in which. Twist1 in infiltrating inflammatory macrophages but not in resident macrophages limited kidney fibrosis after ureteral obstruction by driving extracellular matrix degradation. Moreover, deletion of Twist1 in infiltrating macrophages attenuated the expression of MMP13 in CD11b. Twist1 in infiltrating myeloid cells mitigates interstitial matrix accumulation in the injured kidney by promoting MMP13 production, which drives extracellular matrix degradation. These data highlight the complex cell-specific actions of Twist1 in the pathogenesis of kidney fibrosis.

Topics: Actins; Animals; Benzofurans; Collagen Type I; CX3C Chemokine Receptor 1; Disease Models, Animal; Extracellular Matrix; Fibrosis; Gene Expression; Hydroxyproline; Kidney; Kidney Diseases; Macrophages; Macrophages, Peritoneal; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase Inhibitors; Mice; Morpholines; Myeloid Cells; Twist-Related Protein 1; Ureteral Obstruction

Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Hepatitis C, Chronic; Humans; Imidazoles; Kidney Diseases; Quinoxalines; Retrospective Studies; Sulfonamides

Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Hepatitis C, Chronic; Humans; Imidazoles; Kidney Diseases; Quinoxalines; Retrospective Studies; Sulfonamides

The aim of the present study was to investigate the effects of salvianolic acid B on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Continuous infusion of LPS was used to induce a DIC model in rabbits. Treatment with salvianolic acid B (1, 3 or 6 mg/kg) was started simultaneously with LPS infusion (0.5 mg/kg LPS in 60 mL saline; 10 mL/h over a period of 6 h) through the contralateral marginal ear vein. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count and fibrinogen concentration were determined, as were plasma levels of fibrin-fibrinogen degradation products (FDP), alanine aminotransferase (ALT), blood urea nitrogen (BUN), protein C activity, antithrombin III (ATIII) and tumour necrosis factor (TNF)-α concentration. The gradual impairment of haemostatic parameters was induced by continuous infusion of LPS. There were marked increases in APTT, PT, BUN, ALT and plasma TNF-α and marked decreases in the platelet count, fibrinogen, FDP, protein C and ATIII. The intravenous administration of 1, 3 or 6 mg/kg salvianolic acid B attenuated the increases in APTT, PT, BUN, ALT and plasma TNF-α and the decreases in fibrinogen, platelet, FDP, protein C and ATIII induced by LPS infusion. These observations indicate that salvianolic acid B has an effect against LPS-induced DIC in rabbits.

Topics: Animals; Benzofurans; Disseminated Intravascular Coagulation; Gene Expression Regulation; Kidney Diseases; Lipopolysaccharides; Liver Diseases; Male; Rabbits; Tumor Necrosis Factor-alpha

To investigate the effect and mechanism of salvianolic acid B (SA-B) on renal interstitial fibrosis in rats induced by unilateral ureteral obstruction (UUO).. 18 male SD rats were randomly divided into 3 groups, 6 in each group. After the models were established, the rats were treated with SA-B for 2 weeks. Then their renal pathology were examined by hight microscope and electron microscopy Protein expression levels of alpha-smooth muscle actin (alpha-SMA) and E-cadherin (E-cad) in the obstructed kidney were analyzed by Western blot and Biochemistry assay.. Pathological examination of the kidney in model group showed tubules lumen widened and many inflammatory cells infiltrated, a part of renal tubule expanded and part of them atrophied. The tubular epithelial cells were karyorrhexis or karyolysis, some tubulars were atrophy. The protein expression of alpha-SMA were significantly up-regulated (P < 0.01) and E-cad were significantly down-regulated (P < 0.01) in the model group. After intervention with SA-B, the renal pathological status in the treatment group was significantly improved, the expression of alpha-SMA were significantly down-regulated (P < 0.05), but E-cad only a little up-regulated (P > 0.05).. SA-B could antagonize renal interstitial fibrosis mainly by maintaining epithelial phenotype, inhibiting the protein of alpha-SMA which is the principal effect cells that are responsible for the progressive kidney fibrosis.

Topics: Actins; Animals; Benzofurans; Blotting, Western; Cadherins; Disease Models, Animal; Fibrosis; Immunohistochemistry; Kidney; Kidney Diseases; Kidney Tubules; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Ureteral Obstruction

The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

Topics: Adrenergic alpha-2 Receptor Antagonists; Agmatine; Animals; Benzofurans; Imidazoles; Imidazoline Receptors; Kidney Diseases; Male; Norepinephrine; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sympathetic Nervous System; Veins; Yohimbine

To investigate the effect of salvianolic acid B (SA-B) on renal interstitial fibrosis due to unilateral ureteral obstruction.. Thirty-six SD male rats were randomly divided into 3 groups, 12 in each group, the sham-operated group, the model group and the SA-B treated group. The rat model of renal interstitial fibrosis was successfully established by unilateral ureteral obstruction (UUO). Rats in the SA-B treated group was intragastrically administrated with SA-B (12.5 mg x kg(-1)) daily after modeling. Rats of each group were killed respectively at day 14 and day 21 after UUO. Pathological changes of renal tissue were observed by hematoxylin and eosin (HE) staining. The expression of alpha-smooth muscle actin (alpha-SMA) in kidney was determined with immunohistochemistry. And the expressions of cytokeratinl9 (ck19) mRNA in renal tissue were detected using reverse transcription polymerase chain reaction (RT-PCR).. Renal interstitial fibrosis was obviously ameliorate in SA-B treated group. The expression of alpha-SMA was significantly decreased in SA-B treated group as compared with that in model group at day 14. And the expression of ck19 was significantly lower than that determined in model group at day 21.. SA-B could ameliorate renal interstial fibrosis due to UUO, probable by inhibiting epithelial-to-myofibroblast transdifferentiation and the activation of myofibroblast.

Topics: Animals; Benzofurans; Disease Models, Animal; Drugs, Chinese Herbal; Fibroblasts; Fibrosis; Gene Expression; Humans; Keratin-19; Kidney Diseases; Male; Muscle, Smooth; Random Allocation; Rats; Rats, Sprague-Dawley

The effect of a high fat diet (HFD) on renal function, renal mitochondrial function and intrarenal oxygen-free radial scavenging activity were examined in the ischemia-reperfusion model of the rat kidney. Whether of not a novel lipophilic antioxidant (BO653) could minimize this effect in vivo was also investigated. Thirty minutes renal ischemia was introduced by vascular clamp in rats with or without HFD (cholesterol 1.25%). Some of the HFD rats received BO653 by gastric gavage. Creatinine clearance (Ccr) was measured 24 hours following the injury. Mitochondrial oxygen consumption and thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and alpha-tocopherol were measured in the kidney before, 30 min ischemia and 30 min after reperfusion. HFD significantly reduced Ccr after ischemia-reperfusion (45% decreased compared to normal diet), which was ameliorated by BO653. Thirty-minute ischemia deteriorated the mitochondrial function in the normal diet (ND) group, high fat diet (HFD) group and high fat diet + BO653 (HFD + BO) group. Thirty-minute reperfusion ameliorated the mitochondrial function in all those groups. The kidney content of TBARS was not increased after the ischemia-reperfusion in all these groups. In the HFD group, the kidney content of GPX was higher than in the ND group during ischemia-reperfusion, but in the HFD group, the kidney content of SOD was significantly decreased after the thirty-minute ischemia. Thirty-minute ischemia decreased the kidney content of alpha-tocopherol in the HFD group, which was recovered by the thirty-minute reperfusion. In conclusion, a high fat diet deteriorates ischemia-reperfusion injury of the rat kidney and BO653 ameliorated this effect judged by creatinine clearance and renal mitochondrial function. Reperfusion injury could not be confirmed in the present model based on the results of lipid peroxidation and oxygen-free radical scavenging enzyme activity.

Topics: Animals; Antioxidants; Benzofurans; Dietary Fats; Free Radical Scavengers; Kidney Diseases; Rats; Rats, Wistar; Reperfusion Injury; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Four cases of amiodarone-induced restrictive, hypoxaemic lung disease are described. The cumulative dosages of amiodarone were relatively low (30 to 100 g). Alveolar lavage studies showed a lymphocytosis and study of the lymphocytic sub-populations showed an increase in the OKT8 group, and an inversion of the OKT4/OKT8 ratio. The outcome was favourable on withdrawal of amiodarone and steroid therapy. The immunological origin of this form of lung disease was confirmed. Two patients had renal failure; in the first case, hypercalcaemia, hyperphosphoremia and renal calcification were observed. The second patient had endo- and extracapillary glomerulonephritis with C3 deposits and circulating immune complexes. Renal failure regressed in both cases on withdrawal of amiodarone and with steroid therapy.

Topics: Acute Kidney Injury; Aged; Amiodarone; Benzofurans; Drug Hypersensitivity; Female; Humans; Kidney Diseases; Lymphocytes; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Fibrosis; Therapeutic Irrigation

The effect of the uricosuric drug benzdromarone was investigated in 15 patients with hyperuricemia and renal failure. Benzbromarone micron was given in a dose of 80 mg/day for 6 days. The mean serum uric acid level fell from 8.9 to 4.24 mg/100 ml. After therapy uric acid concentrations in serum returned to 5.2 mg/100 ml. Renal urate elimination was increased from 487 mg/day to 831.3 mg/day; after medication urate elimination decreased to the initial values. Uric acid clearance was increased by benzbromarone from 3.97 to 11.1 ml/min, and even after therapy a uric acid clearance of 6.4 ml/min could be measured. A decrease of uric acid reabsorption from 4.73 to 2.3 mg/min was observed, after medication the reabsorption rate increased to 3.42 mg/min.

Topics: Adult; Aged; Benzbromarone; Benzofurans; Creatinine; Drug Evaluation; Gout; Humans; Kidney Diseases; Male; Middle Aged; Uric Acid

Topics: Benzofurans; Gout; Humans; Kidney Diseases; Probenecid

Topics: Adult; Benzofurans; Biliary Tract Diseases; Colic; Female; Humans; Kidney Diseases; Male; Middle Aged; Vasodilator Agents