Current Issue : October - December Volume : 2017 Issue Number : 4 Articles : 5 Articles
A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N\n-(adamantan-1-yl)-morpholine-4-carbothioimidates 7aââ?¬â??e and 4-arylmethyl (Z)-N-(adamantan-1-yl)-4\n-phenylpiperazine-1-carbothioimidates 8aââ?¬â??e were prepared via the reaction of N-(adamantan-1-\nyl)morpholine-4-carbothioamide 5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide\n6 with benzyl or substituted benzyl bromides, in acetone, in the presence of anhydrous potassium\ncarbonate. The structures of the synthesized compounds were confirmed by 1H-NMR, 13C-NMR,\nelectrospray ionization mass spectral (ESI-MS) data, and X-ray crystallographic data. The in vitro\nantimicrobial activity of the new compounds was determined against certain standard strains of\npathogenic bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 7b, 7d and\n7e displayed potent broad-spectrum antibacterial activity, while compounds 7a, 7c, 8b, 8d and 8e\nwere active against the tested Gram-positive bacteria. The in vivo oral hypoglycemic activity of the\nnew compounds was carried on streptozotocin (STZ)-induced diabetic rats. Compounds 7a, 8ab, and\n8b produced potent dose-independent reduction of serum glucose levels, compared to the potent\nhypoglycemic drug gliclazide....
Background: Salvianolate lyophilized injection (SLI) has been clinically used in China for the treatment of acutely\ncerebral infarction. Clinical and experimental studies have shown that Diabetes mellitus (DM) not only increases the\nrisk of ischemic stroke recurrence but also leads to poor outcomes and increases fatality rates after stroke. Our previous\nstudy has proved that SLI can reduce the infarct volume after stroke in type 1 diabetic rats. The aim of the study is to\nexplore the mechanism of SLI on stroke outcome in type 1 diabetic (T1DM) rats.\nMethods: Type 1 diabetes rats model (T1DM) was induced in male Wistar rats by intraperitoneal (i.p) injection of\nstreptozotocin (60 mg/kg) and T1DM rats were subjected to intraluminal middle cerebral artery occlusion (MCAO). The\nT1DM + MCAO rats were randomly divided into six groups: sham-operated, model-vehicle, positive control group\n(Edaravone-treating, DE 6 mg/kg) and SLI-treating group (10.5 mg/kg, 21 mg/kg and 42 mg/kg). SLI and DE were\nadministered by tail vein injection at 3 h after MCAO, then daily for 14 days. Micro-CT scans of the brain tissue\nrevealed vessel characteristics and distribution in the ischemia zone. Glucose uptake was analyzed by PET/CT. RAGE,\nMMP9 and inflammatory factors (COX-2, TNF-�± and ICAM-1), HQ-1, HQO-1 and Nrf-2 expression levels in the ischemic\nbrain tissue were analyzed by Immunofluorescence staining and Western blot at 14 days after MCAO.\nResults: In this study, we have demonstrated that SLI treatment significantly increased the number of brain\nmicrovasculature in ipsilateral and glucose uptake in cortex, hippocampus and penumbra in the T1DM + MCAO\nrats. SLI also significantly decreased the expression of RAGE, MMP9 and inflammatory factors expression, and\nincreased the expression of HQ-1, HQO-1 and Nrf-2 in T1DM + MCAO rats.\nConclusion: The study showed that SLI could protect against cerebral ischemia injury in T1DM + MCAO rats\nand the mechanism is related to decrease inflammatory factors and activate of the Nrf2/HO-1 signaling pathway....
Ethoxidine, a benzo[c]phenanthridine derivative, has been identified as a potent inhibitor\nof topoisomerase I in cancer cell lines. Our group has reported paradoxical properties of ethoxidine\nin cellular processes leading to angiogenesis on endothelial cells. Because low concentration\nethoxidine is able to favor angiogenesis, the present study aimed to investigate the ability of 10âË?â??9 M\nethoxidine to modulate neovascularization in a model of mouse hindlimb ischemia. After inducing\nunilateral hindlimb ischemia, mice were treated for 21 days with glucose 5% or with ethoxidine,\nto reach plasma concentrations equivalent to 10ââ?¬â??9 M. Laser Doppler analysis showed that recovery\nof blood flow was 1.5 fold higher in ethoxidine-treated mice in comparison with control mice.\nFurthermore, CD31 staining and angiographic studies confirmed an increase of vascular density\nin ethoxidine-treated mice. This ethoxidine-induced recovery was associated with an increase of\nNO production through an enhancement of eNOS phosphorylation on its activator site in skeletal\nmuscle from ischemic hindlimb. Moreover, real-time RT-PCR and western blots have highlighted that\nethoxidine has pro-angiogenic properties by inducing a significant enhancement in vegf transcripts\nand VEGF expression, respectively. These findings suggest that ethoxidine could contribute to favor\nneovascularization after an ischemic injury by promoting the NO pathway and VEGF expression....
The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis\ndrug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced\nliver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral\nadministration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical\nand histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity\nof antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1\nactivity were determined by ELISA assay and liquid chromatographyââ?¬â??tandem mass spectrometry\n(LCââ?¬â??MS/MS) analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF) were\nassessed byWestern blotting. As a result, bicyclol significantly protected against anti-TB drug-induced\nliver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic\nlipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of\nbicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative\nstress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of\nHGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant\neffect on the plasma pharmacokinetics of the anti-TB drug in rats....
Background: Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has\nbeen a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin\nagainst nephrotoxicity induced by cisplatin in rats.\nMethods: Forty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group\nintraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin\ngroup orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys\nwere harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK),\nMitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis\nfactors alpha (TNF-�±), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-�±).\nResults: The cisplatin single dose administration to rats induced nephrotoxicity associated with a significant\nincrease in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in\nkidney tissues by 230 �± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a\nsignificant increase in the expression levels of the IL-1�± (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%)\n, JNK (680%) and TNF-�± (300%) genes compared to control group. Additionally, histopathological examination\nshowed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute\ntubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in\ngene expression and structural and functional changes in the kidney. Additionally, histopathological examination of\nkidney tissues confirmed gene expression data.\nConclusion: The present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent\nCP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK\nsignaling pathways, and repairing the histopathological changes against cisplatin administration....
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