Showing papers on "Intraperitoneal injection published in 2007"
TL;DR: M marrow stromal cells protect the kidney from toxic injury by secreting factors that limit apoptosis and enhance proliferation of the endogenous tubular cells, suggesting that transplantation of the cells themselves is not necessary.
Abstract: Emerging evidence suggests that the intravenous injection of bone marrow-derived stromal cells (BMSC) improves renal function after acute tubular injury, but the mechanism of this effect is controversial. In this article, we confirm that intravenous infusion of male BMSC reduced the severity of cisplatin-induced acute renal failure in adult female mice. This effect was also seen when BMSC (or adipocyte-derived stromal cells (AdSC)), were given by intraperitoneal injection. Infusion of BMSC enhanced tubular cell proliferation after injury and decreased tubular cell apoptosis. Using the Y chromosome as a marker of donor stromal cells, examination of multiple kidney sections at one or four days after cell infusion failed to reveal any examples of stromal cells within the tubules, and only rare examples of stromal cells within the renal interstitium. Furthermore, conditioned media from cultured stromal cells induced migration and proliferation of kidney-derived epithelial cells and significantly diminished cisplatin-induced proximal tubule cell death in vitro. Intraperitoneal administration of this conditioned medium to mice injected with cisplatin diminished tubular cell apoptosis, increased survival, and limited renal injury. Thus, marrow stromal cells protect the kidney from toxic injury by secreting factors that limit apoptosis and enhance proliferation of the endogenous tubular cells, suggesting that transplantation of the cells themselves is not necessary. Identification of the stromal cell-derived protective factors may provide new therapeutic options to explore in humans with acute kidney injury.
478 citations
TL;DR: The results show that augmented glial coupling is one of the major events occurring in DRG following inflammation, and provides indirect support for the idea that augmented intercellular coupling might contribute to chronic pain.
Abstract: Neurons in dorsal root ganglia (DRG) are surrounded by an envelope of satellite glial cells (SGCs). Little is known about SGC physiology and their interactions with neurons. In this work, we investigated changes in mouse DRG neurons and SGC following the induction of inflammation in the hind paw by the injection of complete Freund's adjuvant (CFA). The electrophysiological properties of neurons were characterized by intracellular electrodes. Changes in coupling mediated by gap junctions between SGCs were monitored using intracellular injection of the fluorescent dye Lucifer yellow. Pain was assessed with von Frey hairs. We found that two weeks after CFA injection there was a 38% decrease in the threshold for firing an action potential in DRG neurons, consistent with neuronal hyperexcitability. Injection of Lucifer yellow into SGCs revealed that, compared with controls, coupling by gap junctions among SGCs surrounding adjacent neurons increased 2.7-, 3.2-, and 2.5-fold one week, two weeks, and one month, respectively, after CFA injection. In SGCs enveloping neurons that project into the inflamed paw this effect was more enhanced (5.4-fold). Interneuronal coupling was augmented by up to 7% after CFA injection. Pain threshold in the injected paw decreased by 13%, 16%, and 11% compared with controls at one week, two weeks, and one month, respectively, after CFA injection. Intraperitoneal injection of the gap junction blocker carbenoxolone prevented the inflammation-induced decrease in pain threshold. The results show that augmented glial coupling is one of the major events occurring in DRG following inflammation. The elevation in pain threshold after carbenoxolone administration provides indirect support for the idea that augmented intercellular coupling might contribute to chronic pain.
180 citations
TL;DR: Evidence is provided that MSCs are a valuable source of cells for liver repair and regeneration and that, by the alteration of the site of injection, the generation of hepatocytes occurs in different hepatic zones, suggesting that a combined transplantation approach may be necessary to successfully repopulate the liver with these cells.
151 citations
TL;DR: The effects of intravenous and intracerebroventricular IL-1 are mediated by endothelial IL- 1R1, whereas the effects of intraperitoneal IL-2 are partially dependent on endothelialIL-1R1.
Abstract: Interleukin-1 (IL-1) has been implicated as a critical mediator of neuroimmune communication. In the brain, the functional receptor for IL-1, type 1 IL-1 receptor (IL-1R1), is localized primarily to the endothelial cells. In this study, we created an endothelial-specific IL-1R1 knockdown model to test the role of endothelial IL-1R1 in mediating the effects of IL-1. Neuronal activation in the hypothalamus was measured by c-fos expression in the paraventricular nucleus and the ventromedial preoptic area. In addition, two specific sickness symptoms, febrile response and reduction of locomotor activity, were studied. Intracerebroventricular injection of IL-1 induced leukocyte infiltration into the CNS, activation of hypothalamic neurons, fever, and reduced locomotor activity in normal mice. Endothelial-specific knockdown of IL-1R1 abrogated all these responses. Intraperitoneal injection of IL-1 also induced neuronal activation in the hypothalamus, fever, and reduced locomotor activity, without inducing leukocyte infiltration into the brain. Endothelial-specific knockdown of IL-1R1 suppressed intraperitoneal IL-1-induced fever, but not the induction of c-fos in hypothalamus. When IL-1 was given intravenously, endothelial knockdown of IL-1R1 abolished intravenous IL-1-induced CNS activation and the two monitored sickness symptoms. In addition, endothelial-specific knockdown of IL-1R1 blocked the induction of cyclooxygenase-2 expression induced by all three routes of IL-1 administration. These results show that the effects of intravenous and intracerebroventricular IL-1 are mediated by endothelial IL-1R1, whereas the effects of intraperitoneal IL-1 are partially dependent on endothelial IL-1R1.
147 citations
TL;DR: Histochemical and immunohistochemical analysis of tumor xenografts demonstrated a significant, dose‐dependent decrease in fractions of proliferating cells and an increase in the incidence of apoptosis of cancer cells in mice treated with either GSK‐3β inhibitor.
Abstract: The authors' recent discovery that glycogen synthase kinase-3beta (GSK-3beta) participates in colon cancer cells' survival and proliferation prompted us to investigate whether GSK-3beta inhibition alters proliferation of colon cancer cells in vivo. Groups of four or five athymic mice (Balb/c, nu/nu) with subcutaneous xenografts of SW480 human colon cancer cells were treated with dimethyl sulfoxide (DMSO) or different doses (1, 2 and 5 mg/kg body weight) of either small-molecule GSK-3beta inhibitor (SB-216763 and AR-A014418) by intraperitoneal injection three times per week for 5 weeks. Compared with DMSO (a diluent of the GSK-3beta inhibitors) as a control, either GSK-3beta inhibitor significantly inhibited proliferation of cancer cell xenografts in the rodents in a dose-dependent manner. Histochemical and immunohistochemical analysis of tumor xenografts demonstrated a significant, dose-dependent decrease in fractions of proliferating cells and an increase in the incidence of apoptosis of cancer cells in mice treated with either GSK-3beta inhibitor. No adverse events or effects were observed in the rodents during the course of treatment, except for rare lethal accidents due to intraperitoneal injection. Morphological examination showed no apparent pathologic changes in major organs including the lungs, liver, pancreas, kidneys, spleen and large bowel of rodents treated with DMSO and the GSK-3beta inhibitors. The results indicate that the GSK-3beta inhibitors would be a novel class of therapeutic agent for colon cancer.
138 citations
TL;DR: It is concluded that high-dose rEpo is detectable in brain for >20 h after a single systemic injection, and these pharmacokinetic data are valuable for planning of rEPO neuroprotection experiments.
Abstract: Recombinant human erythropoietin (rEpo) is neuroprotective in neonatal models of brain injury. Pharmacokinetic data regarding the penetration of circulating rEpo into brain tissue is needed to optimize neuroprotective strategies. We sought to determine the pharmacokinetics of rEpo given intraperitoneally or subcutaneously in plasma and brain. We hypothesized that 1) exogenous rEpo would penetrate the blood-brain barrier (BBB), 2) brain and plasma Epo would correlate, and 3) brain injury would enhance rEpo penetration. Two hundred and eighty-four 7-d-old control, sham, or brain-injured rats were treated with i.p. or s.c. rEpo (0, 250, 2500, or 5000 U/kg) and killed at scheduled intervals. Plasma and brain tissue were collected. Epo concentrations were measured by ELISA. Intraperitoneal injection yielded a faster and greater peak concentration of plasma rEpo (Tmax 3 h, Cmax 10,016 ± 685 mU/mL) than s.c. injection (Tmax 9 h, Cmax 6224 ± 753 mU/mL). Endogenous brain Epo was below detection even after hypoxia exposure. Systemic rEpo crossed the BBB in a dose-dependent manner, peaked in brain at 10 h, and was increased after brain injury. We conclude that high-dose rEpo is detectable in brain for >20 h after a single systemic injection. These pharmacokinetic data are valuable for planning of rEpo neuroprotection experiments.
127 citations
TL;DR: The findings of the present experimental animal study indicate that QCT treatment has beneficial effects on pancreatic tissues subjected to STZ-induced oxidative stress by directly quenching lipid peroxides and indirectly enhancing production of endogenous antioxidants.
Abstract: This study was undertaken to investigate the protective effects of quercetin (QCT) on the morphology of pancreatic beta-cells against diabetes mellitus and oxidative stress experimentally-induced by streptozotocin (STZ) treatment in Wistar rats. Fifty male and female Wistar rats (200-250 g) were randomly divided into three experimental groups (i. e., control, STZ-treated, and STZ + Quercetin-treated groups). Diabetes was induced in the diabetic groups (B and C) of animals, by a single intraperitoneal injection of STZ (75 mg/kg), while each of the rats in the 'control' group received equal volume of citrate buffer (pH 6.3) solution intraperitoneally. In group C rats, quercetin (QCT, 25 mg/kg/day i.p.) was injected daily for 3 days prior to STZ treatment, and QCT administration continued until the end of the study period (30 days). Diabetes mellitus was confirmed by using Bayer's Glucometer Elite and compatible blood glucose test strips. The rats were sacrificed serially until the end of the study period (after 30 days). The pancreases of the sacrificed rats were excised and randomly processed for histological staining and biochemical assays for antioxidant enzymes [such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and serum nitric oxide (NO)]. In the diabetic state, pancreatic beta-cells of STZ-treated group B rats histologically demonstrated an early chromatin aggregation, cytoplasmic vesiculation in the central beta-cells, nuclear shrinkage, and lysis of beta-cells with distortion of granules. The morphology of QCT-treated rats' pancreases showed viable cellularity with distinct beta-cell mass. STZ treatment significantly decreased (p<0.05) GSHPx, SOD, CAT and pancreatic insulin content. However, STZ treatment increased blood glucose concentrations, MDA and serum NO. The QCT-treated group of animals showed a significant decrease (p<0.05) in elevated blood glucose, MDA and NO. Furthermore, QCT treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as pancreatic insulin contents. Quercetin (QCT) treatment protected and preserved pancreatic beta-cell architecture and integrity. In conclusion, the findings of the present experimental animal study indicate that QCT treatment has beneficial effects on pancreatic tissues subjected to STZ-induced oxidative stress by directly quenching lipid peroxides and indirectly enhancing production of endogenous antioxidants.
106 citations
Journal Article•
TL;DR: Findings indicate that administration of the dose over the course of days (DOX2 or weeks) results in a better survival rate and more classic signs of DOX-induced dilated cardiomyopathy, albeit with later onset, as compared with a single 10 mg/kg bolus injection of Doxorubicin.
Abstract: The chemotherapeutic agent doxorubicin (DOX) is associated with a dose-dependent cardiotoxicity that can eventuate into heart failure. This study aimed to characterize the onset and degree of cardiotoxicity in rats receiving 10 mg/kg DOX administered as a single intraperitoneal injection (DOX1), 10 daily intraperitoneal injections of 1 mg/kg (DOX2), or in 5 weekly intraperitoneal injections of 2 mg/kg (DOX3). Transthoracic echocardiography measurements were recorded every week to characterize the onset and degree of cardiotoxicity in the 3 groups. An 80% mortality rate was observed at day 28 in DOX1, whereas DOX2 and DOX3 reached 80% mortality at days 107 and 98, respectively. Fractional shortening decreased by 30% at week 2 in DOX1, 55% at week 13 in DOX2, and 42% at week 13 in DOX3. In addition, cardiac function clearly differed between DOX1 and DOX3, whereas DOX2 and DOX3 were similar. These findings indicate that administration of the dose over the course of days (DOX2) or weeks (DOX3) results in a better survival rate and more classic signs of DOX-induced dilated cardiomyopathy, albeit with later onset, as compared with a single 10 mg/kg bolus injection of DOX.
106 citations
TL;DR: In this paper, the authors investigated the effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidant enzymes of weanling pigs, and concluded that injection with diquat would induce more serious oxidative stress than oral intake of oxidized fish oil in the diet.
Abstract: This study was undertaken to investigate the effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidant enzymes of weanling pigs. In the experiment, 24 male LandrancexYorkshire weanling pigs were allotted to three groups of 8 animals each. Pigs were fed individually. According to a single factorial arrangement, pigs received diets with 5% of either fresh (group 1 and group 3) or oxidized fish oil (peroxide value was 786.50 meq O 2 /kg before inclusion in the diet, group 2). At the beginning of the experiment, pigs in group 3 received an intraperitoneal injection of diquat at 12 mg/kg of body weight. The trial lasted for 26 d. A metabolism test was carried out during the last 4 days of the second week. The results showed that feeding diets containing oxidized fish oil or injection with diquat depressed the growth performance and nutrient digestibilities of weanling pigs, decreased activities of antioxidant enzymes and increased concentration of malondialdehyde in plasma and liver. Intraperitoneal injection of diquat would induce more serious oxidative stress than oral intake of oxidized fish oil in the diet. In conclusion, administration of oxidized fish oil or diquat could induce oxidative stress in weanling pigs, and oxidative stress could depress growth performance and impact anti-oxidative ability of young pigs.
102 citations
TL;DR: A role of TNF-α in the pathogenesis of diabetic nephropathy is suggested and the effects of infliximab and FR167653 on urinary albumin excretion are shown to be a potential therapeutic strategy.
Abstract: The objective is to assess the effect of TNF-α inhibition on urinary albumin excretion in experimental diabetic rats. Male Wistar rats, 8-week-old, were categorized into four groups, which were the control (n = 9), diabetes (n = 9), infliximab-treated diabetes (n = 10), and FR167653-treated diabetes (n = 9) groups. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg). Thereafter, infliximab was injected intraperitoneally once a month (5.5 mg/kg) and FR167653 was administered orally by mixing with the rat chow (0.08%). The effects of infliximab and FR167653 on urinary albumin excretion were observed for 12 weeks. Body weight, blood sugar, 24-h urinary TNF-α, and 24-h urinary albumin/creatinine ratio (Ualb/Ucr) levels were determined at 1, 4, 8, and 12 weeks after the STZ-injection. Treatment of rats with STZ caused a significant loss of body weight, as well as polyuria and hyperglycemia within 1 week, while the urinary excretions of albumin and TNF-α were increased. Neither infliximab nor FR167653 affected body weight or blood sugar levels, whereas both decreased urinary albumin excretion, together with a modest decrease in the urinary excretion of TNF-α. These results suggest a role of TNF-α in the pathogenesis of diabetic nephropathy and show that TNF-α inhibition is a potential therapeutic strategy.
96 citations
TL;DR: The results demonstrate the potential of siRNA as a systemic therapeutic option in vivo for selected disease processes and demonstrate differential siRNA uptake depending on delivery technique.
TL;DR: It is suggested that the long circulation, bioavailability and localization of RBLPL in tumor and ascites sites, which also demonstrate that the ip administration of R BLPL is a potential multifunctional nanoradiotherapeutics and imaging agents on a C26 colon carcinoma ascites mouse model.
TL;DR: Intraperitoneal injection of CoPP alleviated disease symptoms, such as joint swelling, cartilage degradation, and proliferation of inflammatory tissue in joints, in the acute phase of inflammatory arthritis in mice, providing the first evidence that pharmacologically induced up-regulation of HO-1 triggers a robust protective antiinflammatory response in a model of nonautoimmune arthritis in animals.
Abstract: Objective
To determine the consequences of pharmacologic up-regulation of heme oxygenase 1 (HO-1), and inhibition of HO-1 by injection of an anti–HO-1 small interfering RNA (siRNA), in vivo in the acute phase of a mouse model of nonautoimmune arthritis.
Methods
In the K/BxN mouse serum transfer model, which mimics human inflammatory arthritis without lymphocyte influence, HO-1 was up-regulated by intraperitoneal injection of cobalt protoporphyrin IX (CoPP), a potent pharmacologic inducer, and was inhibited using a specific siRNA. The clinical progress of arthritis was monitored by measurement of paw thickness. Interleukin-1β (IL-1β), IL-6, tumor necrosis factor α (TNFα), serum antioxidant, and nitric oxide (NO) levels, prostaglandin E2 (PGE2) production, and matrix metalloproteinase 9 (MMP-9) activity were measured in serum. At the end of the experiments, joints were examined for immunohistopathologic changes.
Results
Intraperitoneal injection of CoPP alleviated disease symptoms, such as joint swelling, cartilage degradation, and proliferation of inflammatory tissue in joints, in the acute phase of inflammatory arthritis. The CoPP-induced expression of HO-1 in the joints and liver was associated with marked decreases in IL-1β, IL-6, and TNFα levels, PGE2 secretion, and MMP-9 activity in serum, and with a marked increase in systemic antioxidant activity. In contrast, NO production in serum and inducible NO synthase expression in chondrocytes were not affected by HO-1 induction. Specific inhibition of HO-1 by in vivo delivery of anti–HO-1 siRNA repressed the protective effects.
Conclusion
Our data provide the first evidence that pharmacologically induced up-regulation of HO-1 triggers a robust protective antiinflammatory response in a model of nonautoimmune arthritis in mice. This suggests that exogenously induced HO-1 may have potential as therapy in the acute phase of inflammatory arthritis in humans.
TL;DR: Enantioselective analysis showed that (+)-PCB 136 was enriched in most organs, with the most pronounced enrichment found in the liver and the brain of animals dosed orally or by intraperitoneal injection, respectively.
TL;DR: It is strongly demonstrated that RHO is able selectively to attenuate stress-induced anorexia, providing functional evidence of claimed adaptogen and anti-stress properties of Rhodiola rosea L.
Abstract: Rhodiola rosea L. is one of the most popular adaptogen and anti-stress plants in European and Asiatic traditional medicine. Its pharmacological properties appear to depend on its ability to modulate the activation of several components of the complex stress-response system. Exposure to both physical and psychological stress reduces feeding in rodents. The aim of this work was thus to determine whether in rats an hydroalcoholic R. rosea extract standardized in 3% rosavin and 1% salidroside (RHO) reverses hypophagia induced by (1) physical stress due to 60 min immobilization; (2) intracerebroventricular injection of corticotrophin-releasing factor (CRF, 0.2 microg/rat), the major mediator of stress responses in mammals; (3) intraperitoneal injection of Escherichia coli Lipopolysaccharide (LPS, 100 microg/kg); (4) intraperitoneal administration of fluoxetine (FLU, 8 mg/kg). The effect of the same doses of the plant extract was also tested in freely-feeding and in 20 h food-deprived rats. RHO was administered acutely by gavage to male Wistar rats 1 h before the experiments. The results show that at 15 and 20 mg/kg, RHO reversed the anorectic effects induced both by immobilization and by intracerebroventricular CRF injection. Moreover, at the same doses, RHO failed to reduce the anorectic effect induced both by LPS and FLU, and did not modify food intake in both freely-feeding and food-deprived rats. These findings strongly demonstrated that RHO is able selectively to attenuate stress-induced anorexia, providing functional evidence of claimed adaptogen and anti-stress properties of Rhodiola rosea L.
TL;DR: Observations indicate that intraperitoneal DEP injection does not induce inflammation or oxidatively damaged DNA in the lung and aorta, whereas a direct effect in terms of inflammation and oxidized DNA was observed in the liver of dyslipidemic ApoE(-/-) mice.
TL;DR: The authors investigated the location of the cecum in adult male and female albino and pigmented rat populations, and evaluated the consequences of intraperitoneal injections in the right and left portion of the lower abdomen.
Abstract: Intraperitoneal injection is a common route for parenteral administration of drugs in rodents. A serious consequence associated with this technique, however, is the puncture of vital organs such as the cecum, which causes pain and occasionally peritonitis. Reports have described the cecum as located on either side of the lower abdominal cavity, contributing to the idea that intraperitoneal injections can be performed in either side. The authors investigated the location of the cecum in adult male and female albino and pigmented rat strains, and evaluated the consequences of intraperitoneal injections in the right and left portion of the lower abdomen. Of the rats they investigated, 71.8% had ceca on the left side of the abdomen. The authors also found that injections on the left side were more likely to result in punctured ceca.
TL;DR: The sucrose breath test detected damage induced by 5-FU and is a simple, noninvasive indicator of small bowel injury and the probiotics assessed offered no protection from mucositis at the dose tested.
Abstract: The sucrose breath test (SBT) was employed to noninvasively assess the efficacy of probiotics in 5-fluorouracil (5-FU)-induced intestinal mucositis. Dark Agouti rats were allocated to 5 groups (n=10): 5-FU+L. fermentum BR11, 5-FU+L. rhamnosus GG, 5-FU+B. lactis BB12, 5-FU+skim milk (SM), and saline+SM. Probiotics were administered by oral gavage for 10 days. Mucositis was induced on day 7 by intraperitoneal injection of 5-FU (150 mg/kg) or vehicle (saline). Rats were sacrificed 72 h after 5-FU injection. The SBT measured breath 13CO2 (expressed as percentage cumulative dose at 90 min; %CD90) on days 0, 7, and 10. %CD90 was significantly lower in 5-FU-treated controls compared with that in saline-treated controls on day 10. 5-FU caused an 83% reduction in sucrase and a 510% increase in MPO activity. The SBT detected damage induced by 5-FU and is a simple, noninvasive indicator of small bowel injury. The probiotics assessed offered no protection from mucositis at the dose tested.
TL;DR: The results support that the carcinogenicity of furan is caused by a non-genotoxic mechanism and not a significant increase in the micronucleus frequency after treatment with furan.
TL;DR: Results correlate with previous normal rat studies, and demonstrate potential use of this avidin/biotin-liposome system for prolonging drug delivery to the peritoneal cavity and associating lymph nodes in this ovarian cancer xenograft model.
TL;DR: The results suggest that the strain L. salivarius CECT5713 is nonpathogenic for mice, even in doses 10,000 times higher (expressed per kilograms of body weight) than those normally consumed by humans.
TL;DR: Systemic VD(3) therapy delays carcinogenesis in the hamster buccal pouch model of carcinogenesis and may lead to development of effective chemopreventive agents to combat head and neck cancer.
Abstract: Objective To investigate whether systemic therapy with 1-alpha,25-dihydroxyvitamin D 3 (vitamin D 3 [hereinafter, VD 3 ]) prevents tumor formation in a hamster buccal pouch model of carcinogenesis. Design Randomized trial in which a known carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was applied to the buccal pouch of 40 hamsters. Animals were randomized to receive systemic VD 3 or no treatment and killed at 2, 6, and 14 weeks after the initiation of DMBA exposure. Setting Academic medical center. Subjects Forty male golden Syrian hamsters, aged 5 to 6 weeks, were used. Interventions A dose of 0.25 μg/kg of VD 3 via intraperitoneal injection was given to 20 animals 3 times per week. Of the remaining 20 control animals, 5 received placebo vehicle injection, and 15 received no further treatment. Main Outcome Measures Timing, size, and number of tumors that developed in the 2 groups. Results Only 1 hamster treated with VD 3 developed a confirmed neoplasm compared with 7 of the control animals ( P 3 -treated group was 1.2 ± 1.9 mm compared with 6.8 ± 6.6 mm in the control group ( P = .03). The time to onset of lesion formation was significantly delayed in those animals treated with VD 3 , with a mean ± SD time to development of 13.4 ± 0.9 weeks, while the control animals developed lesions at 11.2 ± 1.7 weeks ( P = .02). Conclusions Systemic VD 3 therapy delays carcinogenesis in the hamster buccal pouch model. Further investigation into the mechanisms through which VD 3 inhibits carcinogenesis may lead to development of effective chemopreventive agents to combat head and neck cancer.
TL;DR: The results of this study suggest that mixed tocopherols may be safe and effective agents for the prevention of breast cancer.
Abstract: Tocopherols are present in significant amounts in vegetable oils used in human foods. The most prevalent tocopherols in foods are the α, β, γ, and δ variants with (RRR) stereochemistry. Tocopherols are lipophilic phenolic antioxidants, produced by plants. In the United States, γ -tocopherol is the most prominent dietary tocopherol due to its high amount in the dominant commercially produced vegetable oils such as soybean, corn, and cottonseed. In this report, experiments were designed to study the inhibitory effect of mixed tocopherols against N-methyl-N-nitrosourea-induced mammary tumor growth in female Sprague-Dawley rats. Beginning at 21 days of age, rats were treated with a single intraperitoneal injection of 50 mg/kg body weight of N-methyl-N-nitrosourea. One wk later, the rats were fed experimental diets containing 0 or 0.1% mixed tocopherols containing over 50% γ -tocopherol. At 9 wk after N-methyl-N-nitrosourea treatment, all rats were evaluated for inhibition of mammary tumor growth and ...
TL;DR: In this article, an experimental animal model, intraperitoneal injection of aminolevulinic acid (ALA) and hexylester of AMI (He-ALA), were compared in order to improve laparoscopic detection of ovarian peritoneal carcinomatosis.
Abstract: The goal of this study was to assess the interest of photodynamic diagnosis (PDD) for laparoscopic detection of peritoneal micro metastasis in ovarian carcinoma. Using an experimental animal model, intraperitoneal injection of aminolevulinic acid (ALA) and hexylester of aminolevulinic acid (He-ALA) were compared in order to improve laparoscopic detection of ovarian peritoneal carcinomatosis. Twenty-one 344 Fischer female rats received an intra peritoneal injection of 10 6 NuTu-19 cells. At day 22, carcinomatosis with micro peritoneal metastasis was obtained. Rats were randomized in three groups concerning intra peritoneal injection before laparoscopic staging: 5-ALA hydrochloride, HE-ALA and sterile water. Using D Light system®, laparoscopic peritoneal exploration was performed with white light (WL) first and then with blue light (BL). The main objective was to assess feasibility and sensibility of laparoscopic PDD for nonvisible peritoneal micro metastasis of ovarian cancer. The main parameter was the confirmation of neoplasic status of fluorescent foci by histology. Concerning PDD after intraperitoneal injection of 5-ALA, mean values of lesions seen is higher than without fluorescence (32 vs 20.7; P = 0.01). Using He-ALA, mean values of detected lesions is higher than without fluorescence (42.9 vs 33.6; P < 0.001). Neoplasic status of fluorescent foci was confirmed in 92.8% of cases (39/42). Using 5-ALA, fluorescence of cancerous tissue is significantly higher than that of normal tissue in all the rats (ratio 1.17) (P = 0.01). With He-ALA, intensity of fluorescence is significantly higher in cancerous tissue compared to normal tissue, irrespective of the rat studied (ratio 1.22; P < 0.001).
TL;DR: It is shown here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested.
Abstract: Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested.
TL;DR: In conclusion, intraperitoneal injection of sodium pentobarbitone caused a significant increase in nociception which was lowered by adding lidocaine to the formulation, although it was still significantly higher than the control level.
Abstract: After a search on Medline, it appears that intraperitoneal injection of sodium pentobarbitone is often used for anaesthesia and euthanasia of rodents. In the present pilot study in rats, spinal nociception after intraperitoneal injection of sodium pentobarbitone, with and without lidocaine, was examined by estimation of the number of c-fos-expressing neurones in the spinal dorsal horn. One group of rats received an intraperitoneal injection of 0.4 mL/kg sodium pentobarbitone (100 mg/mL; n=4). Another group of rats received a similar intraperitoneal injection of sodium pentobarbitone formulated with lidocaine 10 mg/mL (n=4); a control group received a similar intraperitoneal injection of 0.9% saline (n=4). After 3 h, the animals were re-anaesthetized and perfused with 4% formaldehyde, and the spinal cord was collected and processed by immunohistochemistry for stereological quantification of the number of neurones with c-fos-like immunoreactivity (FLI). Intraperitoneal injection of the sodium pentobarbitone formulation caused a significantly increased number of neurones with FLI in the spinal cord (3930+/-247; mean+/-SEM; P<0.001) compared with the saline control group (765+/-131). The lidocaine added to the sodium pentobarbitone formulation significantly reduced the number to 2716+/-393 (P<0.05). In conclusion, intraperitoneal injection of sodium pentobarbitone caused a significant increase in nociception which was lowered by adding lidocaine to the formulation, although it was still significantly higher than the control level. Further studies are needed with the aim of optimizing the lidocaine concentration and also to examine the effect of the combination of lidocaine with a long-acting local anaesthetic agent, e.g. bupivacaine.
TL;DR: Melatonin diminished the intestinal oxidative stress and apoptotic damage induced by endotoxemia in infant rats and increased the activities of antioxidant enzymes and attenuated apoptotic cell death in both intestinal epithelium and lamina propria.
Abstract: To evaluate the effect of melatonin on the intestinal apoptosis along with oxidative damage in endotoxemic infant rats. Prospective animal study in a university-based experimental research laboratory. Wistar albino 7-day-old rat pups (n = 21). The animals were randomized into three experimental groups: (1) controls; (2) endotoxemia; (3) endotoxemia treated with melatonin (10 mg/kg). Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (Escherichia coli serotype 0111:B4; 3 mg/kg). Four hours after LPS injection, the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and thiobarbituric acid reactive substance (TBARS) levels as an indicator of lipid peroxidation, were determined. Intestinal apoptosis was assessed by hematoxylin-eosin staining and terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling. The administration of melatonin into endotoxemic rats prevented the increase in the TBARS levels, and increased the activities of antioxidant enzymes and attenuated apoptotic cell death in both intestinal epithelium and lamina propria. Melatonin diminished the intestinal oxidative stress and apoptotic damage induced by endotoxemia in infant rats.
TL;DR: The aim of this study was to observe the changes in expression of IL-1RI and tyrosine hydroxylase (TH), a rate-limiting enzyme for catecholamine synthesis, in the glomus cells of the rat carotid body following intraperitoneal injection ofIL-1β.
Abstract: It is well established that reciprocal modulation exists between the central nervous system and immune system. Interleukin (IL)-1beta, a proinflammatory cytokine secreted at early stage of immune challenge, has been recognized as one of the informational molecules in immune-to-brain communication. However, how this large molecule is transmitted to the brain is still unknown. In recent years it has been reported that the cranial nerves, especially the vagus, may play a pivotal role in this regard. It is proposed that IL-1beta may bind to its corresponding receptors located in the glomus cells of the vagal paraganglia and then elicit action potentials in the nerve. The existence of IL-1 receptor type I (IL-1RI) in the vagal paraganglia has been shown. The carotid body, which is the largest peripheral chemoreceptive organ, is also a paraganglion. We hypothesize that the carotid body might play a role similar to the vagal paraganglia because they are architectonically similar. Recently we verified the presence of IL-1RI in the rat carotid body and observed increase firing in the carotid sinus nerve following IL-1beta stimulation. The aim of this study was to observe the changes in expression of IL-1RI and tyrosine hydroxylase (TH), a rate-limiting enzyme for catecholamine synthesis, in the glomus cells of the rat carotid body following intraperitoneal injection of IL-1beta. The radioimmunoassay result showed that the blood IL-1beta level was increased after the intraperitoneal injection of rmIL-1beta (750 ng/kg) from 0.48+/-0.08 to 0.78+/-0.07 ng/ml (P<0.05). Immunofluorescence and Western blot analysis showed that the expression of IL-1RI and TH in the rat carotid body was increased significantly following peritoneal IL-1beta stimulation. In addition, double immunofluorescence labeling for TH and PGP9.5, a marker for glomus cells, or TH immunofluoresence with hematoxylin-eosin (HE) counterstaining revealed that a considerable number of glomus cells did not display TH immunoreactivity. These data provide morphological evidence for the response of the carotid body to proinflammatory cytokine stimulation. The results also indicate that not all of the glomus cells express detectable TH levels either in normal or in some abnormal conditions.
TL;DR: HSP70-/- mice showed higher alanine transaminase levels and a more severe degree of neutrophilic infiltration and necrosis than those of wild-type mice and recovered more slowly from CCl(4) treatment, suggesting they could be an adequate model of acute liver toxicity study.
TL;DR: It is concluded that FTY720 is an effective anticancer agent for liver tumor in a rat model without affecting the immune system of the host.
Abstract: We aim to investigate the anticancer effect of a novel immunomodulator FTY720 on a rat orthotopic liver tumor model. A buffalo rat orthotopic liver tumor model was established by injection of a buffalo hepatoma cell line MH7777 into the right portal vein. FTY720 was administered by intraperitoneal injection starting at 10 days after tumor cell injection at a dosage of 5 mg/kg/day. FTY720 markedly suppressed tumor growth and inhibited tumor progression by selective induction of apoptosis of tumor cells via down-regulation of phospho-Akt(ser473) and up-regulation of cleaved caspase-3, together with decrease of focal adhesion kinase. Moreover, the proliferation index of tumor cells was significantly reduced to 15.92+/-5.03% by FTY720 compared with that of 42.92+/-4.47% in the control group (p<0.001). In addition, we confirmed that FTY720 caused no effect on infiltrated lymphocyte in tumor tissue. We conclude that FTY720 is an effective anticancer agent for liver tumor in a rat model without affecting the immune system of the host.