Showing papers on "Intraperitoneal injection published in 2009"
TL;DR: The in vivo acute toxicity of nano‐sized TiO2 particles to adult mice was investigated and showed signs of acute toxicity such as passive behavior, loss of appetite, tremor and lethargy, as well as thrombosis found in the pulmonary vascular system.
Abstract: Because of its excellent optical performance and electrical properties, TiO2 has a wide range of applications in many fields. It is often considered to be physiologically inert to humans. However, some recent studies have reported that nano-sized TiO2 may generate potential harm to the environment and humans. In this paper the in vivo acute toxicity of nano-sized TiO2 particles to adult mice was investigated. Mice were injected with different dosages of nano-sized TiO2 (0, 324, 648, 972, 1296, 1944 or 2592 mg kg(-1)). The effects of particles on serum biochemical levels were evaluated at various time points (24 h, 48 h, 7 days and 14 days). Tissues (spleen, heart, lung, kidney and liver) were collected for titanium content analysis and histopathological examination. Treated mice showed signs of acute toxicity such as passive behavior, loss of appetite, tremor and lethargy. Slightly elevated levels of the enzymes alanine aminotransferase and aspartate aminotransferase were found from the biochemical tests of serum whereas blood urea nitrogen was not significantly affected (P < 0.05). The accumulation of TiO2 was highest in spleen (P < 0.05). TiO2 was also deposited in liver, kidney and lung. Histopathological examinations showed that some TiO2 particles had entered the spleen and caused the lesion of spleen. Thrombosis was found in the pulmonary vascular system, which could be induced by the blocking of blood vessels with TiO2 particles. Moreover, hepatocellular necrosis and apoptosis, hepatic fibrosis, renal glomerulus swelling and interstitial pneumonia associated with alveolar septal thickening were also observed in high-dose groups.
329 citations
TL;DR: Results suggest that cold allodynia induced by oxaliplatin is at least partly due to the increased expression of TRPM8 in the primary afferents.
147 citations
TL;DR: Investigation of the effect of beta-glucan on the immune response and its protection against an infection of the bacterial pathogen Aeromonas hydrophila in zebrafish found it modulated IFNgamma and chemokine expression in kidney and enhanced the ability of kidney cells to kill A. hydrophILA.
121 citations
TL;DR: It is demonstrated that europium (III) hydroxide [Eu(III)(OH)(3)] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral isChemic disease.
97 citations
01 Jan 2009
TL;DR: The purpose of this study was to determine species related differences in the diabetogenic response to streptozotocin (STZ) after single intraperitoneal injection in adult, male, nude rats and to assess severity of the induced diabetic state.
Abstract: The purpose of this study was to determine species related differences in the diabetogenic response to streptozotocin (STZ) after single intraperitoneal injection. Twenty adult, male, nude rats (NR, strain Crl:NIH-Fox1 RNU ) and 8 adult, male Sprague-Dawley (SD) rats were used to induce diabetes using streptozotocin. A single, 150mg/kg STZ was injected intraperitoneally in both strains of rats. Four rats (2 from each strain) were injected buffer and served as control. Severity of the induced diabetic state was assessed by daily monitoring of body weights, clinical signs, and blood glucose levels. Four rats in the NR group died in an average of 5 days following STZ injection and 4 rats of the SD group died in an average of 2 days. In the NR group, non fasting serum glucose levels (267 ± 80 mg/dl) rose significantly (P ≤ 0.05) only in 7 (35%) rats while all SD group experienced glucose levels above 300 mg/dl (324 ± 20 mg/dl) and required insulin treatment all over the
96 citations
TL;DR: In addition to rare injection failure, the IP injection of d-luciferin led to the overestimation of signals from IP tissues, and SC injection was shown to be a convenient alternative to IP injection for BLI.
Abstract: We compared subcutaneous (SC) injection and intraperitoneal (IP) injection of d-luciferin for in vivo bioluminescence imaging (BLI) to determine the utility of SC injection. Mice bearing SC tumours stably expressing firefly luciferase underwent in vivo BLI using SC and IP injection of d-luciferin. BLI studies were repeated at an interval of 3 h using a given injection route to assess repeatability and using different injection routes to assess correlation. In mice bearing both SC and IP tumours, BLI was performed successively using intravenous (IV), SC, and IP injection of d-luciferin. Haematological malignancy model mice underwent BLI using SC and IP injection. In SC tumours, the peak time was slightly shorter and the peak signal was greater using SC injection than using IP injection. The repeatability of determining peak signals was comparable between the two injection routes, and a good correlation was observed between them. In mice bearing both SC and IP tumours, signals from IP tumours relative to those from SC tumours were much greater using IP injection than using IV or SC injection. In the haematological malignancy model, signals from the spleen relative to those from the bone marrow were greater using IP injection than using SC injection. In addition to rare injection failure, the IP injection of d-luciferin led to the overestimation of signals from IP tissues. For BLI, SC injection was shown to be a convenient alternative to IP injection.
69 citations
TL;DR: Investigation of the effect of dexamethasone (DEX) on acute respiratory distress syndrome induced by the H5N1 viral infection in mice found it has no beneficial effect, and DEX therapy did not inhibit inflammatory cellular infiltration and cytokine release in bronchoalveolar lavage fluid induced by
Abstract: Glucocorticoids are widely used in the treatment of different inflammatory diseases. The present study was performed to investigate the effect of dexamethasone (DEX) on acute respiratory distress syndrome (ARDS) induced by the H5N1 viral infection in mice. BALB/c mice, 6-8 weeks old, were divided into three groups with 80 mice in each. The infected group and the DEX-treated infected group were inoculated intranasally with 1 x 10(2) 50% mouse infectious dose of A/Chicken/Hebei/108/2002 (H5N1) viruses, with daily intraperitoneal injections of PBS, or 2.5 mg.kg(-1) DEX at days 3-14 post inoculation, respectively. The control group received noninfectious allantoic fluid and a daily intraperitoneal injection of PBS. In H5N1-infected mice, DEX treatment did not improve the mortality (17 out of 20 versus 16 out of 20 deaths in the DEX-treated infected group versus the infected group), and did not alleviate clinical signs, including weight loss, decreased food intake and inactivity. There was no significant amelioration of the hypoxaemia and ARDS-associated pathological changes in DEX-treated infected mice, as assessed by blood gas analysis and histological score. Furthermore, DEX therapy did not inhibit inflammatory cellular infiltration and cytokine release (interleukin-6 and tumour necrosis factor-alpha) in bronchoalveolar lavage fluid induced by the H5N1 infection. In conclusion, dexamethasone treatment (2.5 mg.kg(-1)) from days 3-14 post inoculation has no beneficial effect on acute respiratory distress syndrome caused by the H5N1 infection in mice.
63 citations
TL;DR: It is suggested that the ACTIValoe N-931 complex has hepatoprotective effects in both acute and chronic liver injuries induced by CCl(4), as well as in antifibrotic experiments, tissue inhibitor of metalloprotease-1 (TIMP-1) mRNA expression was attenuated by treatment with ACTIVa N- 931 complex.
57 citations
TL;DR: LPS administration through injection and bathing effectively stimulates the non-specific cellular as well as secondary immune response and offers protection against A. hydrophila infection in carps.
56 citations
TL;DR: Results showed that paeoniflorin concentration-dependently down-regulated the levels of TNF-alpha, IL-6 and high-mobility group-box 1 protein in lipopolysaccharide-induced RAW264.7 cell, inhibited the IkappaB kinase pathway and modulated NF-kappaB, and the anti-inflammatory mechanism of pae oniflor in may inhibit activation of the NF- kappaB pathway by inhibiting Ikappa B kin
Abstract: The present study was carried out to investigate the effects of paeoniflorin in cultured RAW264.7 cell line as well as in an experimental model of sepsis induced by cecal ligation and puncture, and intraperitoneal injection (i.p.) of lipopolysaccharide in rats. Results showed that paeoniflorin concentration-dependently down-regulated the levels of TNF-alpha, IL-6 and high-mobility group-box 1 protein in lipopolysaccharide-induced RAW264.7 cell, inhibited the IkappaB kinase pathway and modulated NF-kappaB. Intravenous injection (i.v.) of paeoniflorin alone or in combination with imipenem reduced i.p. of lipopolysaccharide or cecal ligation and puncture-induced lethality in rats. In addition, serum levels of TNF-alpha, IL-6, high-mobility group-box 1 protein, triggering receptor expressed on myeloid cells and endotoxin were down-regulated; by contrast, serum levels of IL-10 were up-regulated. Amelioration of hemodynamics, decrease of enzyme levels, decrease of myeloperoxidase in lung, liver, and small intestine were also found after paeoniflorin injection. These data indicate that the anti-sepsis effect of paeoniflorin was mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. This work provides the first evidence that paeoniflorin has the capacity to inactivate inflammatory response in sepsis and the anti-inflammatory mechanism of paeoniflorin may inhibit activation of the NF-kappaB pathway by inhibiting IkappaB kinase activity.
54 citations
TL;DR: Zigzag changes in oxidative enzymes in liver of crucian carp after intraperitoneally injection with extracted microcystins contributed a better understanding on oxidative stress caused by microcyStins in fish.
Abstract: This study was conducted to investigate time-dependent changes in oxidative enzymes in liver of crucian carp after intraperitoneally injection with extracted microcystins 600 and 150 μg kg−1 body weight. The results showed that activities of antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase generally exhibited a rapid increase in early phase (1–3 h post injection), but gradually decreased afterwards (12–48 h) compared with the control, with an evident time-dependent effect. These zigzag changes over time contributed a better understanding on oxidative stress caused by microcystins in fish.
TL;DR: Investigation of the efficacy of ozone therapy in the prevention of Mtx-induced intestinal injury in rats found that the HIS, antioxidant enzyme and MDA levels of the ileal tissue were significantly lower in the ozone treated group than the untreated group.
Abstract: Methotrexate (Mtx) is an effective chemotherapeutic agent used in various cancer treatments. Gastrointestinal toxicity is the drug's major limiting factor, arising mainly from oxidative damage. It has been proposed that ozone (O(3)) is an activator of antioxidant enzymes. Thus, this study was designed to investigate the efficacy of ozone therapy in the prevention of Mtx-induced intestinal injury in rats. Twenty rats were allocated into three groups: sham, Mtx alone (untreated) and Mtx + O(3) (treated with ozone). Ozone was administered at a dose of 0.72 mg/kg daily via an intraperitoneal route for 15 d. On d 16, Mtx was applied via an intraperitoneal injection at a dose of 6 mg/kg for 5 d. All rats were sacrificed at d 21. Efficacy of the treatment was assessed by measuring the histopathologic injury score (HIS), and biochemically by determining tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in ileum, liver and kidney homogenates. Although two rats (25%) died in the untreated group, all rats in the sham and treatment groups survived the study. The HIS, antioxidant enzyme and MDA levels of the ileal tissue were significantly lower in the ozone treated group than the untreated group (p 0.05). Thus, ozone preconditioning shows a preventative effect in the ileum by decreasing tissue damage and increasing antioxidant enzyme activity in an experimental model of Mtx-induced intestinal injury.
Journal Article•
TL;DR: Rutin prevents experimental selenite-induced cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and of GSH, and by inhibiting lipid peroxidation.
Abstract: Purpose: To investigate whether rutin retards selenite-induced cataractogenesis in Wistar rat pups. Methods: On postpartum day ten, Group I rat pups received an intraperitoneal injection of saline. Group II and III rat pups received a subcutaneous injection of sodium selenite. Group III also received an intraperitoneal injection of rutin once daily on postpartum days 9–14. Both eyes of each pup were examined from day 16 up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for mean activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase. In addition, the mean concentrations of reduced glutathione (GSH) and of malondialdehyde were analyzed in samples of lenses and hemolysate. Results: There was dense lenticular opacification in all of Group II, minimal opacification in 33.3% of Group III, no opacification in 66.7% of Group III, and no opacification in Group I. Significantly lower mean activities of lenticular antioxidant enzymes were noted in Group II, compared to Group I and III. Significantly lower mean concentrations of GSH and higher mean concentrations of malondialdehyde were noted in samples of hemolysate and lens from Group II, compared to the values in Group I and III. Conclusion: Rutin prevents experimental selenite-induced cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and of GSH, and by inhibiting lipid peroxidation.
TL;DR: After subcutaneous or intraperitoneal injection of 14C-pentachloro-phenol (14C-PCP) in the mouse the distribution of the activity in the body was determined by whole-body autoradiography and by analysis of the individual organs after oxidation to 14CO2, showing that there is both a gastric and a biliary secretion of PCP and/or its metabolites, and excretion in the faeces.
Abstract: After subcutaneous or intraperitoneal injection of 14C-pentachloro-phenol (14C-PCP) in the mouse (specific activity 1.6 μci/mg, dose 15–37 mg/kg body weight) the distribution of the activity in the body was determined by whole-body autoradiography and by analysis of the individual organs after oxidation to 14CO2. The highest specific activity was found in the gall bladder and its contents, the wall of the stomach fundus, the contents of the gastro-intestinal tract and the liver. This shows that there is both a gastric and a biliary secretion of PCP and/or its metabolites, and excretion in the faeces. Most of the activity (72–83 %) was excreted in the urine in four days, about half of the dose in 24 hours. Only traces (< 0.05 %) were detected in the expired air. Identification and estimation of metabolites were performed by paper chromatography and isotope dilution techniques. All the urinary activity in the first 24 hours was due to PCP and probably tetrachlorohydroquinone. At least PCP was excreted in both the free and the conjugated form.
TL;DR: The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-β, IL-6,IL-13 and IFN-γ.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Leukotrienes play an important role in IPF, and leukotriene (LT)B(4) is one of the key eicosanoids in IPF. In this study, we investigated whether ONO-4057, a LTB(4) receptor (BLTR) antagonist is capable of preventing bleomycin-induced pulmonary fibrosis. On day 1, C57BL/6 male mice were given a single intratracheal injection of bleomycin (2.5 mg x kg(-1)), and ONO-4057 (1.0 mg x kg(-1)) or vehicle alone, administered by intraperitoneal injection on days 1-5 each week for 3 weeks after the bleomycin injection. ONO-4057 reduced the total cell count in bronchoalveolar lavage fluid (BALF) on days 7, 14 and 21 and the Ashcroft score and the lung hydroxyproline content on days 14 and 21. The LTB(4), interleukin (IL)-6, IL-13, transforming growth factor (TGF)-beta levels in BALF and the TGF-beta expression in lung tissue, assessed by immunohistochemistry were decreased on day 7, whereas interferon (IFN)-gamma level in BALF was increased on day 14. The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-beta, IL-6, IL-13 and IFN-gamma.
TL;DR: It is found that bile HMGB1 mediates gut barrier dysfunction in experimental endotoxemia and feeding endotoxemic rat bile to normal mice significantly increased both mucosal permeability and bacterial translocation.
Abstract: Lipopolysaccharide (LPS) is an important factor in sepsis. LPS given by intraperitoneal injection induces intestinal hyperpermeability and bacterial translocation in animals and stimulates hepatic ...
TL;DR: It is suggested that administration of OX at a high dose and for a long term enhances oxidative stress responses, which may contribute to its tumor-promoting potential in rats.
Abstract: The tumor-promoting effects of oxfendazole (OX), a benzimidazole anthelmintic, were investigated using a medium-term rat hepatocarcinogenesis model. Six-week-old male F344 rats received an intraperitoneal injection of N-diethylnitrosamine (DEN) and were given a powdered diet containing 0 or 500 ppm OX for 6 weeks from 2 weeks after DEN treatment. All animals were subjected to two-thirds partial hepatectomy 1 week after OX treatment. The numbers and areas of glutathione S-transferase placental form (GST-P)-positive foci were significantly increased in the livers of rats treated with OX, with concomitantly increased cell proliferation, compared with those in the livers of the DEN alone group. Quantitative real-time RT-PCR analysis revealed that OX induced not only mRNA expression of phase I enzymes Cyp1a1, Cyp1a2, but also Nrf2-regulated phase II enzymes such as Gpx2, Nqo1, Yc2, Akr7a3 and Gstm1, presumably due to an adaptive response against OX-induced oxidative stress. Reactive oxygen species production increased in microsomes isolated from the livers of OX-treated rats. Furthermore, OX enhanced oxidative DNA damage (as assessed by 8-hydroxydeoxyguanosine; 8-OHdG) and lipid peroxidation (as assessed by thiobarbituric acid-reactive substances; TBARS). These results suggest that administration of OX at a high dose and for a long term enhances oxidative stress responses, which may contribute to its tumor-promoting potential in rats.
TL;DR: It is shown that critically ill patients who were on antiplatelet drugs (aspirin or clopidogrel) for secondary prevention of cardiovascular events developed organ failure less frequently and had lower mortality than patients without such pre-existing medication.
TL;DR: A very good correlation between brain biochemistry and behavioural effects of MeHg was observed, that is, the dose response relationship for the open field task correlated with alterations in levels of metabolic intermediates.
Abstract: The effects on mouse behaviour in the open field situation of controlled single doses of methyl mercury (MeHg) (1, 5, 10 mg Hg/kg) were investigated at varying times after intraperitoneal injection (1, 3, 72 hours). In an effort to correlate behavioural and biochemical data, the effects of dose and time after dose on the levels of selected glycolytic pathway intermediates, a-glycerophosphate, adenine nucleotides and phosphocreatine were monitored. A very good correlation between brain biochemistry and behavioural effects of MeHg was observed. That is, the dose response relationship for the open field task correlated with alterations in levels of metabolic intermediates. At 1 and 3 hours after administration of MeHg, when the levels of the metabolic intermediates were significantly different from those of controls, altered behaviour was observed. At 72 hours post administration, when the biological parameters were approaching control values, a return to normal behaviour was observed.
TL;DR: TRPV1 and its main neuropeptides, CGRP and SP, in hearts were impaired during DM, and these changes were essentially reduced in diabetic mice.
TL;DR: Findings provide the proof of principle that RI.TAT-RasGAP(317-326) may be useful for improving the efficacy of chemotherapy in patients and enhance the tumor growth inhibitory effect of cisplatin.
Abstract: Peptides that interfere with the natural resistance of cancer cells to genotoxininduced apoptosis may improve the efficacy of anticancer regimens. We have previously reported that a cell-permeable RasGAP-derived peptide (TAT-RasGAP 317 – 326 ) specifically sensitizes tumor cells to genotoxin-induced apoptosis in vitro. Here, we examined the in vivo stability of a protease-resistant d -form of the peptide, RI·TATRasGAP 317 – 326 , and its effect on tumor growth in nude mice bearing subcutaneous human colon cancer HCT116 xenograft tumors. After intraperitoneal injection, RI·TAT-RasGAP 317 – 326 persisted in the blood of nude mice for more than 1 hour and was detectable in various tissues and subcutaneous tumors. Tumor-bearing mice treated daily for 7 days with RI·TAT-RasGAP 317 – 326 (1.65 mg/kg body weight) and cisplatin (0.5 mg/kg body weight) or doxorubicin (0.25 mg/kg body weight) displayed reduced tumor growth compared with those treated with either genotoxin alone (n = 5 – 7 mice per group; P = .004 and P = .005, respectively; repeated measures analysis of variance [ANOVA, two-sided]). This ability of the RI·TAT-RasGAP 317 – 326 peptide to enhance the tumor growth inhibitory effect of cisplatin was still observed at peptide doses that were at least 150-fold lower than the dose lethal to 50% of mice. These findings provide the proof of principle that RI·TAT-RasGAP 317 – 326 may be useful for improving the efficacy of chemotherapy in patients. J Natl Cancer Inst 2009;101: 828 – 832
TL;DR: Naltrexone significantly reduced ethanol self-administration, and NTX was more potent when administered via subcutaneous injection versus intraperitoneal injection, which further support the notion that NTX acts by terminating responding early rather than reducing the initial responding.
TL;DR: It is evident that STZ‐diabetes has an adverse effect on sperm maturation, which may be due to the decrease in the bioavailability of testosterone and epididymal secretory products.
Abstract: The present study is aimed to explore the impact of experimental diabetes and insulin replacement on epididymal secretory products, sperm count, motility, and fertilizing ability in albino rats. Prepubertal and adult male Wistar strain rats were made diabetic with a single intraperitoneal injection of streptozotocin (STZ), at 120 and 65 mg/kg body weight for prepubertal and adult rats, respectively. After 3 days of STZ administration, insulin was given to a group of diabetic rats at a dose of 3 U/100 g body weight, subcutaneously and killed after 20 days of treatment. STZ-diabetes significantly reduced the epididymal tissue concentrations of testosterone, androgen-binding protein, sialic acid, glycerylphosphoryl choline, and carnitine, suggesting its adverse effects on the secretory activity and concentrating capacity of epididymal epithelium. Impaired cauda epididymidal sperm motility and fertility (in vivo) of STZ-diabetic rats imply the defective sperm maturation. Insulin replacement prevented these changes either partially or completely. From the above findings, it is evident that STZ-diabetes has an adverse effect on sperm maturation, which may be due to the decrease in the bioavailability of testosterone and epididymal secretory products.
TL;DR: Analysis of macrophage response to polycarbonate-urethane, a proposed alternative material to polyethylene in acetabular components of total hip arthroplasty, indicates particles of PCU may be less disruptive to bone-implant fixation than x-UHMWPE in vivo, under both LPS free and challenged conditions.
Abstract: This study was undertaken to examine macrophage response to polycarbonate-urethane, a proposed alternative material to polyethylene in acetabular components of total hip arthroplasty. Polyethylene wear debris from total joint replacements has been linked to osteolysis and implant lifespan. It has been shown in vitro, that polyethylene particles cleaned of endotoxin generate less of an inflammatory cytokine response than endotoxin bound particles. Comparative particle induced effects on implant fixation were tested using endotoxin free cross-linked ultra-high molecular weight polyethylene (x-UHMWPE) and polycarbonate-urethane (PCU) particles with and without intraperitoneal injection (IP) of lipopolysaccharide (LPS) using a Ti-alloy femoral intramedullary nail rat model. MicroCT and mechanical testing assessment of peri-implant bone indicated significantly less bone and lower fixation strength, respectively, when the implant was surrounded by xUHMWPE particles compared to PCU particles (with and without LPS IP). This indicates particles of PCU may be less disruptive to bone-implant fixation than x-UHMWPE in vivo, under both LPS free and challenged conditions.
TL;DR: Intravenous jugular vein injection of siRNA strongly targets the lung tumor and is effective in gene inhibition as demonstrated for Hif-1α and HIF-2α, a well-established HIF target protein.
Abstract: Different routes for the in vivo administration of synthetic siRNA complexes targeting lung tumors were compared, and siRNA complexes were administered for the inhibition of hypoxia-inducible factor (HIF-1α and HIF-2α). Intravenous jugular vein injection of siRNA proved to be the most effective means of targeting lung tumor tissue in the Lewis lung carcinoma (LLC1) model. In comparison, intraperitoneal injection of siRNA was not suitable for targeting of lung tumor and intratracheal administration of siRNA exclusively targeted macrophages. Inhibition of HIF-1α and HIF-2α by siRNA injected intravenously was validated by immunohistofluorescent analysis for glucose-transporter-1 (GLUT-1), a well-established HIF target protein. The GLUT-1 signal was strongly attenuated in the lung tumors of mice treated with siRNA-targeting HIF-1α and HIF-2α, compared with mice treated with control siRNA. Interestingly, injection of siRNA directed against HIF-1α and HIF-2α into LLC1 lung tumor-bearing mice resulted in prolonged survival. Immunohistological analysis of the lung tumors from mice treated with siRNA directed against HIF-1α and HIF-2α displayed reduced proliferation, angiogenesis and apoptosis, cellular responses, which are known to be affected by HIF. In conclusion, intravenous jugular vein injection of siRNA strongly targets the lung tumor and is effective in gene inhibition as demonstrated for HIF-1α and HIF-2α.
TL;DR: It is suggested that emodin has antidiabetic and lipid‐modulating effects that involve, in part, upregulation of L‐type calcium channel expression in the pancreas and heart in dyslipidaemic–diabetic rats.
Abstract: 1. The aim of the present study was to evaluate the hypoglycaemic and hypolipidaemic effects of 20, 40 and 80 mg/kg per day emodin and its potential effects on L-type calcium channels in dyslipidaemic-diabetic rats. 2. Dyslipidaemic-diabetic rats were induced by a single intraperitoneal injection of streptozotocin (55 mg/kg) after intragastric administration of a high-fat diet for 2 weeks. 3. Daily administration of emodin for 2 weeks resulted in a significant dose-dependent reductions in blood glucose, serum total cholesterol, triglycerides, free fatty acids and malonaldehyde (P < 0.05) in dyslipidaemic-diabetic rats compared with vehicle-treated dyslipidaemic-diabetic rats. In addition, emodin caused dose-dependent increases in plasma superoxide dismutase activity in dyslipidaemic-diabetic rats (P < 0.05). Immunofluorescent staining and reverse transcription-polymerase chain reaction showed that the expression of L-type calcium channels in the pancreas and heart was restored, to different extents, by the three doses of emodin treatment. 4. The results of the present study suggest that emodin has antidiabetic and lipid-modulating effects that involve, in part, upregulation of L-type calcium channel expression in the pancreas and heart in dyslipidaemic-diabetic rats.
TL;DR: Administration of heparin–SOD may be useful in the treatment and prevention of acute liver failure and hepatic fibrosis and it is demonstrated that it could markedly attenuate the mRNA expression of TGF-β1, MMP-2, and collagen-I.
Abstract: In this study, the effects of heparin-superoxide dismutase conjugate (heparin-SOD) on carbon tetrachloride (CCl4)-induced acute liver failure and hepatic fibrosis were evaluated. To investigate the effects of heparin-SOD on acute liver failure, heparin-SOD was administered to CCl4-treated mice by intravenous injection. Biochemical indicators, such as glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT), GSH (glutathione), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were determined 24 h after CCl4 treatment. The development of CCl4-induced acute liver failure altered the redox state with a decreased hepatic GSH and increased formation of lipid peroxidative products, which were partially normalized by treatment with heparin-SOD or heparin + SOD. Compared with other groups, the acute liver injury of heparin-SOD group was significantly lessened (reduced activities of GOT/GPT, MDA, and increased activities of GSH). To investigate the effects of heparin-SOD on hepatic fibrosis, heparin-SOD and CCl4 were co-administered by intraperitoneal injection twice a week for 12 weeks. Histological and hepatic hydroxyproline examination revealed that heparin-SOD could significantly prevent the progression of hepatic fibrosis. Moreover, real-time PCR was used to determine transforming growth factor-beta1 (TGF-beta1), metalloproteinase-2 (MMP-2), fibronectin, and collagen-I expression. Significantly, greater fibrosis and TGF-beta1, MMP-2, fibronectin, and collagen-I expression were found in the liver of CCl4-induced mice at the end of 12th week. Heparin-SOD could markedly attenuate the mRNA expression of TGF-beta1, MMP-2, and collagen-I. Western blots of tissue homogenates revealed that the protein expression of TGF-beta1 was substantially reduce also by heparin-SOD treatment. These results demonstrate that administration of heparin-SOD may be useful in the treatment and prevention of acute liver failure and hepatic fibrosis.
TL;DR: In this article, the effects of intraperitoneal injection of four naturally occurring free fatty acids (FFAs) on serum calcium in rats were examined. And the results showed that minute quantities of oleate (100 microliters per 250 g rat) caused marked hypocalcemia (7.2 +/- 0.3 mg/dl).
Abstract: Indirect evidence suggests a causative role for intraperitoneal free fatty acids (FFA) in hypocalcemia associated with pancreatitis. We examined the effects of intraperitoneal injection of four naturally occurring FFAs on serum calcium in rats. Two saturated FFAs, stearate and palmitate, induced little or no hypocalcemia. Two unsaturated FFAs, oleate and linoleate, caused dramatic hypocalcemia in treated versus control rats (6.3 +/- 1.4 and 5.3 +/- 0.7 mg/dl, respectively, versus 10.1 +/- 0.6). Dose-response studies demonstrated that minute quantities of oleate (100 microliters per 250 g rat) caused marked hypocalcemia (7.2 +/- 0.3 mg/dl). Treated versus control rats also revealed a decrease in ionized calcium (3.15 +/- 0.2 versus 5.6 +/- 0.05 mg/dl) and magnesium (1.4 +/- 0.15 versus 2.0 +/- 0.10), an appropriate increase in PTH levels (1670 +/- 451 versus 396 +/- 235 pg/ml), and a fall in calcitonin levels (70.4 +/- 21.3 versus 47.5 +/- 16.4 pg/ml) but no change in albumin or phosphate levels. In vitro, the Ksp of calcium dioleate was shown to be 5.3 x 10(-8) m3/liter3; thus under physiologic conditions 100 microliters oleate binds 7.2 mg calcium, or approximately twice the total ECF ionized calcium in the rat. The amounts of intraperitoneal FFA that can easily be achieved in pancreatitis complex pathophysiologically significant amounts of calcium and may lead to severe hypocalcemia.
TL;DR: The use of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice showed promising results, but further research is needed to determine the mechanism of action.
Abstract: The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1-diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)-1beta, free radicals and nitrogen species, and a corresponding increase in cellular calcium concentration because of ORE were confirmed in bone marrow and spleen dendritic cells that are known to play important functions in the development and advancement of atopic dermatitis (AD). It was thus expected that ORE would exert a beneficial effect in the treatment of AD. A study on the pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We therefore used an in vivo AD animal model, namely the NC/Nga mice, and by applying ORE onto the animals through skin application as well as intraperitoneal injection, we attempted to evaluate the benefits of ORE in this system. Evaluation of ORE was conducted by following the SCORE method to score the effect, as well as by measuring the Th2 cytokines IL-4, IL-5 and IL-13 levels from serum and lymphocytes, and IgE and eosinophil levels from serum. Additionally, the expression of mRNA and protein levels was estimated using real-time polymerase chain reaction and Western blotting analysis. The following categories of clinical evaluation, Th2 cytokines IL-4, IL-5 and IL-13 values, serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels of iNOS and COX-2, were evaluated from topical application and intraperitoneal injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed as being similar to the positive control group, while a significant difference with the negative control group was observed. The results presented in this report suggest that ORE might be beneficial in the treatment of AD.
TL;DR: Western blot analysis of nitrotyrosine failed to show inhibition of free radical production by AA, however, results show that AA inhibits both necrotic and apoptotic cell death and that AA is neuroprotective after HI in immature rat brain.
Abstract: Ascorbic acid (AA) is a potent antioxidant, and its neuroprotective effect has not been established yet. Using the Rice-Vannucci model, we examined the effect of AA on hypoxic-ischemic (HI) injury in the immature rat brain. Under isoflurane anesthesia, 7-day-old rat pups received 750 mg/kg of AA by intraperitoneal injection just before hypoxic exposure; 8% oxygen for 90 min. Vehicle controls received an equal volume of saline. AA decreased a macroscopic brain injury score at 48 and 168 h post-HI compared with vehicle controls (48 h post-HI, AA 1.38+/-0.45 vs. controls 2.94+/-0.24, p<0.05; 168 h post-HI, 1.13+/-0.44 vs. 2.50+/-0.25, p<0.05). AA injection significantly decreased the number of both necrotic and apoptotic cells in cortex, caudate putamen, thalamus and hippocampus, and also seemed to reduce the number of TUNEL-positive cells. Western blot analysis showed that AA significantly suppressed 150/145 kDa subunits of alpha-fodrin breakdown products (FBDP) in cortex, striatum, thalamus and hippocampus at 24 and 48 h post-HI, and also 120 kDa subunit of FBDP in all examined regions except for thalamus, which indicated that AA injection inhibited both calpain and caspase-3 activation. Western blot analysis of nitrotyrosine failed to show inhibition of free radical production by AA, however, our results show that AA inhibits both necrotic and apoptotic cell death and that AA is neuroprotective after HI in immature rat brain.