Current Issue : April - June Volume : 2017 Issue Number : 2 Articles : 6 Articles
Background: Oxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients.\nUntil now, no effective preventive or therapeutic drug has been developed; therefore, the dose-limiting factor of\nOXIPN is still an obstacle in the use of oxaliplatin to treat cancer patients. In the present study, we report for the\nfirst time that the aqueous extract of Lithospermi radix (WLR) can attenuate the OXIPN in both in vitro and in vivo\nneuropathic models.\nMethods: The protective effect of WLR on OXIPN was evaluated in vitro by quantifying nerve growth factor (NGF)-\nstimulated neurite outgrowth in PC12 cells treated with a combination of oxaliplatin and WLR. The neuroprotective\npotential of WLR was further confirmed by measuring the changes in nociceptive sensitivities to external mechanical\nstimuli in neuropathic animals induced by oxaliplatin. Histological and immunohistochemical studies were further done\nto examine the effect of WLR in mouse spinal cords and footpads.\nResults: Oxaliplatin-induced neurotoxicity in NGF-stimulated PC12 cells. It could reduce the lengths and branching\nnumbers of neuritis in NGF-stimulated PC12 cells. Co-treatment of WLR rescued the differentiated PC12 cells from\nthe neurotoxicity of oxaliplatin. In a chronic OXIPN animal model, administration of oxaliplatin i.p. induced enhanced\nnociceptive sensitivity to mechanical stimuli (25.0 to 72.5 % of response rate) along with spinal activation of microglias\nand astrocytes and loss of intraepidermal nerve fibers in footpads, which is remarkably suppressed by oral administration\nof WLR (67.5 to 35 % of response rate at the end of experiment). Cytotoxicity of oxaliplatin determined in human cancer\ncells was not affected irrespective of the presence of WLR.\nConclusions: In conclusion, we demonstrated that WLR can attenuate OXIPN in both in vitro and in vivo experimental\nmodels, which may be in part attributed to its anti-inflammatory activity in the spinal cord and its neuroprotective\npotential in the peripheral nerve system without affecting the anti-tumor potential of oxaliplatin. Therefore, WLR could\nbe considered as a good starting material to develop a novel therapeutic agent targeting OXIPN. However, further\nstudies should be done to elucidate the underlying mechanism such as molecular targets and active constituent(s) in\nWLR with neuroprotective potential....
Electronic cigarettes (e-cigarettes, ECIGs) were introduced into the market a decade ago as an alternative to\ntobacco smoking. Whether ECIGs are safe and whether they qualify as smoking cessation tool is currently unknown.\nTheir use has markedly expanded in that period, despite the fact that potential toxic effects of the vapour created\nby the e-cigarette and the nicotine-containing cartridge fluid have been incompletely studied. Marketing targets\ndiverse groups including older smokers but also young people. Whereas the adverse health effects of nicotine\ninhaled by users of ECIGs has been well documented, less is known about the other components. An increasing\nnumber of in vitro and in vivo studies demonstrate a range of adverse effects of both the vapour created by ECIGs\nas well as the nicotine-containing fluid. Importantly, these studies demonstrate that toxicity from ECIGs, although\nthis may be less than that caused by tobacco products, not only arises from its nicotine content. Furthermore, there\nare no data on the long-term consequences of ECIG use. The wide range of ECIG products available to consumers\nand the lack of standardisation of toxicological approaches towards ECIG evaluation complicates the assessment of\nadverse health effects of their use. Here we review the current data on preclinical studies on ECIGs describing their\neffects in cell culture and animal models....
Grape seed as a fruit waste was found to have medicinal potentials, specially its procyanidine containment. The\npresent work aimed to investigate the anticancer potential against two of the mostly spread cancers worldwide namely breast\nand colon cancers. Data recorded revealed that grape seed extract (GSE) demonstrated a dose dependent cytotoxic potential\nwith an IC50 values of 148.5 and 190.2 Ã?¼g/ml for CaCo-2 and MCF-7 respectively. Gene expression pattern of apoptosis related\ngenes revealed that GSE stimulates a p53-independent apoptotic pathway which was associated with G2/M phase arrest\n(pÃ?â??0.05). The elevated level of reactive oxygen species (ROS) in the order of 28.5% and 40.8% in CaCo-2 and MCF-7,\nrespectively suggested that GSE is involved also in initiating the intrinsic pathway of apoptosis. These findings focus on the\npotential of using GSE as a multi-targeted cancer therapy to overcome the problem of resistance to current treatments....
Background: Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children\nworldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high\nside-effect profile. New therapeutic approaches are urgently needed.\nMethods: Here, we leverage PGC-1�±, a powerful transcriptional coactivator known to protect against dystrophy in\nthe mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy.\nResults: We identify heme oxygenase-1 (HO-1) as a potential novel target for the treatment of DMD. Expression of\nHO-1 is blunted in the muscles from the mdx murine model of DMD, and further reduction of HO-1 by genetic\nhaploinsufficiency worsens muscle damage in mdx mice. Conversely, induction of HO-1 pharmacologically protects\nagainst muscle damage. Mechanistically, HO-1 degrades heme into biliverdin, releasing in the process ferrous iron\nand carbon monoxide (CO). We show that exposure to a safe low dose of CO protects against muscle damage in\nmdx mice, as does pharmacological treatment with CO-releasing molecules.\nConclusions: These data identify HO-1 and CO as novel therapeutic agents for the treatment of DMD. Safety\nprofiles and clinical testing of inhaled CO already exist, underscoring the translational potential of these\nobservations....
Background: Animal models of para-renal cancer can provide useful information for the evaluation of tumor\nresponse to loco-regional therapy experiments in solid tumors. The aim of our study was to establish a rabbit\npara-renal cancer model using locally implanted VX2 tumors.\nMethods: In order to generate a rabbit model of para-renal cancer, we established four hind limb donor rabbits by\nusing frozen VX2 tumor samples. Following inoculation, rabbits were monitored for appetite and signs of pain.\nViable tumors appeared as palpable nodules within 2 weeks of inoculation. Tumor growth was confirmed in all\nrabbits by high-resolution ultrasound analysis and histology. Once tumor growth was established, hind limb tumors\nextraction was used for tumor line propagation and para-renal tumor creation. Twenty-one rabbit models bearing\npara-renal cancer were established by implanting VX2 tumor into the para-renal capsula. Tumors developed into\ndiscreet 2ââ?¬â??3 cm nodules within 1ââ?¬â??3 weeks of implantation. Serial renal ultrasonography follow-up, starting 1 week\nafter tumor implantation, was performed. Two weeks after tumor implantation, rabbits were euthanized and tumors\nand other organs were collected for histopathology.\nResults: Tumor growth after VX2 tumor fragment implantation was confirmed in all rabbits by high-resolution\nultrasound (US) imaging examinations of the para-renal regions and was measured with digital caliper. The\npara-renal injection of VX2 tumor fragments, achieved tumor growth in 100% of cases. All data were confirmed by\nhistological analysis.\nConclusions: We generated for the first time, a model of para-renal cancer by surgical tumor implantation of\nVX2 frozen tumor fragments into rabbitââ?¬â?¢s para-renal region. This method minimizes the development of\nmetastases and the use of non-necrotic tumors and will optimize the evaluation of tumor response to loco-regional\ntherapy experiments....
Hyperkalemia is one of the most important risk factors in patients suffering from\ncrush syndrome with rhabdomyolysis. Glycerol-injected animals have been used as\nan experimental model of rhabdomyolysis-induced acute kidney injury (AKI), but\nlittle information is available for the onset and molecular mechanism of hyperkalemia.\nIn our murine model, plasma potassium levels increased after a single injection\nof 50%-glycerol solution (10 ml/kg, i.m.) during the progression of muscular and\nrenal injuries. Renal tubular Na+-K+-ATPase functions as ion-exchange pomp for\npotassium clearance from blood into renal tubular epithelial cells. Renal histochemistry\nrevealed an apparent decrease in the tubular Na+-K+-ATPase expression, especially\nat 24 hours post-glycerol challenge in our AKI model. In contrast to the loss in\nactive Na+-K+-ATPase, there was a significant increase in the renal levels of transforming\ngrowth factor-�² (TGF-�²) that is known to suppress Na+-K+-ATPase production\nin vitro . When anti-TGF-�² antibody was administered in mice after the glycerol\nchallenge, the suppression of renal Na+-K+-ATPase activity was partially restored. As\na result, hyperkalemia was improved in the TGF-�²-neutralized AKI mice, associated\nwith a significant decrease in plasma potassium concentration. Taken together, we\npredict that endogenous TGF-�² is a key regulator for inhibiting Na+-K+-ATPase\nproduction and, in part, enhancing hyperkalemia during progression of rhabdomyolysis-\ninduced AKI. This is, to our knowledge, the first report to determine a critical\nrole of endogenous TGF-�² in renal potassium metabolism during crush syndrome....
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