Showing papers on "Intraperitoneal injection published in 2011"

Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats

Abstract: Scope: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-α and PKC-β1 activity-ERK1/2 pathway. Methods and results: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 wk. At 11 wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-α and PKC-β1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-β1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. Conclusion: These results prove that curcumin produces dual blockade of both PKC-α and PKC-β1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.

Effects of administration route, dietary condition, and blood glucose level on kinetics and uptake of 18F-FDG in mice.

Abstract: The effects of dietary condition and blood glucose level on the kinetics and uptake of 18 F-FDG in mice were systematically investigated using intraperitoneal and tail-vein injection. Methods: Dynamic PET was performed for 60 min on 23 isoflurane-anesthetized male C57BL/6 mice after intravenous (n 5 11) or intraperitoneal (n 5 12) injection of 18F-FDG. Five and 6 mice in the intravenous and intraperitoneal groups, respectively, were kept fasting overnight (18 6 2h ), and the others were fed ad libitum. Serial blood samples were collected from the femoral artery to measure 18 F-FDG and glucose concentrations. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. The standardized uptake valu e( SUV) was estimated from the 45- to 60-min image. The metabolic rate of glucose (MRGlu) and 18 F-FDG uptake constant (Ki) were derived by Patlak graphical analysis. Results: In the brain, SUV and Ki were significantly higher in fasting mice with intraperitoneal injection, but MRGlu did not differ significantly under different dietary states and administration routes. Cerebral Ki was inversely related to elevated blood glucose levels, irrespective of administration route or dietary state. In myocardium, SUV, Ki, and MRGlu were significantly lower in fasting than in nonfasting mice for both routes of injection. Myocardial SUV and Ki were strongly dependent on the dietary state, and Ki did not correlate with the blood glucose level. Similar results were obtained for skeletal muscle, although the differences were not as pronounced. Conclusion: Intraperitoneal injection is a valid alternative route, providing pharmacokinetic data equivalent to data from tail-vein injection for small-animal 18F-FDG PET. Cerebral Ki varies inversely with blood glucose level, but the measured cerebral MRGlu does not correlate with blood glucose level or dietary condition. Conversely, the Ki values of the myocardium and skeletal muscle are strongly dependent on dietary condition but not on blood glucose level. In tissue in which 18 F-FDG uptake

Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice.

Abstract: Kisspeptin is distributed in brain areas regulating reproduction but also in nuclei involved in feeding control. Whether kisspeptin alters food intake is unknown in mice. We examined how kisspeptin-10 influences feeding after intracerebroventricular injection in mice using automated monitoring. Kisspeptin-10 (0.3, 1 and 3µg/mouse) dose-dependently inhibited the feeding response to an overnight fast by 50%, 95% and 90% respectively during the 2–3 h period post injection. The 1µg/mouse dose reduced the 4-h cumulative food intake by 28% while intraperitoneal injection (10µg/mouse) did not. The decreased 4-h food intake was due to reduced meal frequency (−45%/4h), whereas meal size and gastric emptying were not altered. These data suggest that kisspeptin may be a negative central regulator of feeding by increasing satiety.

Propranolol uptake into the central nervous system and the effect on rat behaviour and amine metabolism.

Abstract: Propranolol readily penetrated all areas of the central nervous system after acute intraperitoneal administration and was cleared within 8–16 hr. Propranolol levels in the heart followed a similar pattern. After chronic oral administration brain levels of propranolol were equal to those 3 hr after intraperitoneal injection. Propranolol caused no significant difference in the brain levels of noradrenaline, normetanephrine, dopamine, 3-methoxytyramine, homovanillic acid, 5-hydroxy-tryptamine or total indoles, nor did it cause measurable changes in rat behaviour. An increase by propranolol in sleeping time after chloral hydrate in rats and mice was observed; this effect could not be correlated with changes in brain amine concentrations.

Maslinic acid, a natural inhibitor of glycogen phosphorylase, reduces cerebral ischemic injury in hyperglycemic rats by GLT‐1 up‐regulation

Abstract: Maslinic acid (MA), a natural triterpene from Olea europaea L., is a well-known inhibitor of glycogen phosphorylase and elicits multiple biological activities. The purpose of this study was to evaluate the effects of MA on focal cerebral ischemia in hyperglycemic rats. Adult rats were made hyperglycemic by intraperitoneal injection of streptozotocin and were given MA (50 mg/kg or 5 mg/kg) intragastrically for 14 consecutive days. Transient middle cerebral artery occlusion/reperfusion was then induced by a suture insertion technique. Results showed that diabetic rats pretreated with high-dose MA had lower blood glucose levels, but both doses reduced infarct volumes and improved neurological scores. Less glutamate overflow was also observed in MA-treated rats after 2 hr of ischemia followed by 24 hr and 72 hr reperfusion. In addition, MA treatment enhanced the glial glutamate transporter GLT-1 expression at the protein and mRNA levels. However, the injection of dihydrokainate, a GLT-1 glutamate transporter inhibitor, reversed the effect of MA. Previous studies have shown that suppression of glutamate uptake via nuclear factor-κB (NF-κB) activation is an important contributory factor in ischemia-triggered glutamate excitotoxicity, and inhibition of NF-κB could prevent ischemic suppression of glutamate uptake and GLT-1 expression. In the present study, we showed that MA pretreatment attenuated ischemia-induced translocation of NF-κB p65 subunit to the nucleus. In conclusion, these findings demonstrate that, in addition to showing promising antidiabetic properties, MA has a direct beneficial effect in cerebral ischemic injury, which may be correlated with the promotion of glutamate clearance by NF-κB-mediated GLT-1 up-regulation. © 2011 Wiley-Liss, Inc.

Biochemical and pathological studies on the effects of levamisole and chlorambucil on Ehrlich ascites carcinoma-bearing mice.

Abstract: Clinicopathological studies on the effects of combining immunostimulant drugs (levamisole) with anti-cancer drugs (chlorambucil) revealed the enhancement of the latter against Ehrlich ascites carcinoma-bearing mice and resulted in a reduction in the size of tumour. An evaluation of liver and kidney functions showed a significant increase of alanine transaminase (ALT), aspartate transaminase (AST) and creatinine in all groups. Histopathological studies of one group that received an intraperitoneal injection of Ehrlich ascites carcinoma cells (2.5 × 10⁶) showed that hepatic parenchyma revealed degenerative changes. The portal area was oedematous and showed rounded cell aggregations. Cell death within hypertrophied Kupper cells was observed in some hepatic cells. The neoplastic emboli could be seen either inside blood vessels or hepatic sinusoids, while another group which had been treated orally with a combination of Leukeran(™) (0.2 mg/kg body weight) and levamisole (5 mg/kg body weight) revealed that hepatic parenchyma revealed massive necrosis with proliferative bile duct epithelium. No neoplastic cells were observed without the hepatic parenchyma, while the renal cortex presented a large number of lymphocytes and plasma cells forming bands or aggregates, mainly around the blood vessels. It was concluded that the addition of levamisole to chlorambucil improved the anti-cancer effect of chlorambucil against Ehrlich ascites carcinoma. However, it had adverse effects on the liver and kidneys as shown by liver and kidney function tests and confirmed by histopathology.

Pancreas-protective effects of chlorella in STZ-induced diabetic animal model: insights into the mechanism

Abstract: The aim of this study is to examine the effect of intragastric administration of chlorella (1 g/kg body weight) for a period of 30 days to treat normal and diabetic male Wistar rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg - 1 body weight). A significant (p < 0.05) reduction of blood glucose level in diabetic chlorella-treated rats was observed compared to diabetic untreated. Chlorella increased the number of glutathione-positive cell in diabetic rats compared to untreated diabetics. Chlorella administration increased the percentage of insulin secreting pancreatic beta cells both in normal and diabetic treated rats. Percentage of glucagon producing alpha cells of the pancreas were reduced both in normal and diabetic chlorella-treated rats. Chlorella-induced regenerative ability on pancreas was mediated by up-regulation of Ki67 and down-regulation of P53 and by its potent anti-oxidant ability. The present results suggest that chlorella may play an important role in improving the overall condition of diabetic patients and delay its complication by restoring the function of pancreatic insulin-secreting cells.

Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy (HIPEC).

Abstract: Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death in the USA. Recurrence rates are high after front-line therapy and most patients eventually die from platinum (Pt) - resistant disease. Cisplatin resistance is associated with increased nucleotide excision repair (NER), decreased mismatch repair (MMR) and decreased platinum uptake. The objective of this study is to investigate how a novel combination of sodium arsenite (NaAsO2) and hyperthermia (43°C) affect mechanisms of cisplatin resistance in ovarian cancer. We established a murine model of metastatic EOC by intraperitoneal injection of A2780/CP70 human ovarian cancer cells into nude mice. We developed a murine hyperthermic intraperitoneal chemotherapy model to treat the mice. Mice with peritoneal metastasis were perfused for 1 h with 3 mg/kg cisplatin ± 26 mg/kg NaAsO2 at 37 or 43°C. Tumors and tissues were collected at 0 and 24 h after treatment. Western blot analysis of p53 and key NER proteins (ERCC1, XPC and XPA) and MMR protein (MSH2) suggested that cisplatin induced p53, XPC and XPA and suppressed MSH2 consistent with resistant phenotype. Hyperthermia suppressed cisplatin-induced XPC and prevented the induction of XPA by cisplatin, but it had no effect on Pt uptake or retention in tumors. NaAsO2 prevented XPC induction by cisplatin; it maintained higher levels of MSH2 in tumors and enhanced initial accumulation of Pt in tumors. Combined NaAsO2 and hyperthermia decreased cisplatin-induced XPC 24 h after perfusion, maintained higher levels of MSH2 in tumors and significantly increased initial accumulation of Pt in tumors. ERCC1 levels were generally low except for NaAsO2 co-treatment with cisplatin. Systemic Pt and arsenic accumulation for all treatment conditions were in the order: kidney > liver = spleen > heart > brain and liver > kidney = spleen > heart > brain respectively. Metal levels generally decreased in systemic tissues within 24 h after treatment. NaAsO2 and/or hyperthermia have the potential to sensitize tumors to cisplatin by inhibiting NER, maintaining functional MMR and enhancing tumor platinum uptake.

Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice.

Abstract: Routine laboratory procedures, such as handling or transporting animals or carrying out injections on animals, are stressful for animals but are necessary in many pre-clinical studies. Here, the authors show that multiple injections of the non-toxic vehicle cyclodextrin moderately increased plasma corticosterone concentrations in female BALB/c mice. Additionally, male BALB/c mice that had received a single intraperitoneal injection of harmless saline had an increased glucocorticoid response to a second saline injection. The authors found that female mice that had been exposed to an acute psychological stress session had a decreased glucocorticoid response to a second homotypic stressor. In contrast, multiple psychological stress sessions led to increased glucocorticoid release in female mice. Acute injection(s) of saline in male mice and of cyclodextrin in female mice led to transient lymphocytopenia. Further analysis showed that repeated stress-induced lymphocytopenia is glucocorticoid-dependent. The authors conclude that laboratory stress can affect physiological parameters in mice, potentially altering study results.

Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine

Abstract: Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intraperitoneal injection of saline or amphetamine (1.0, 2.0 or 4.0 mg/kg). Seven days later, half of the mice from the saline group received a second injection of saline. The remaining animals were challenged with 2.0 mg/kg amphetamine. Following all of the injections, mice were placed in activity chambers and locomotion was quantified for 45 min. The magnitude of both the acute and sensitized locomotor stimulatory effect of amphetamine was higher in the adolescent mice. Previous experience with the test environment inhibited the acute amphetamine stimulation in both adolescent and adult mice, but facilitated the detection of elevated spontaneous locomotion in adolescent animals. These results support the notion that the adolescent period is associated with an increased risk for development of drug abuse. Additionally, they indicate a complex interaction between the environmental novelty, adolescence and amphetamine.

Berberine Improves Glucose Homeostasis in Streptozotocin-Induced Diabetic Rats in Association with Multiple Factors of Insulin Resistance

Abstract: The present study was carried out to determine the effect of berberine on glucose homeostasis and several biomarkers associated with insulin sensitivity in male Wistar rats with intraperitoneal injection of streptozotocin (STZ)-induced diabetes. Rats with fasting blood glucose 16.7 mmol/L after 2 weeks of STZ injection were divided into two groups. One group was used as the diabetic control and another treated by gavage feeding with 100 mg/kg/d of berberine in water containing 0.5% carboxymethyl cellulose. A group of rats without receiving STZ was used as the normal control. After 7 weeks, berberine supplementation moderately but significantly lowered fasting blood glucose levels and improved oral glucose tolerance. Berberine lowered plasma free fatty acids and C-reactive protein levels without affecting plasma insulin levels. Diabetic rats treated with berberine showed significantly lower plasma triacylglycerol and cholesterol levels. Furthermore, berberine inhibited dipeptidyl peptidase-4 and protein tyrosine phosphatase-1B activities. In conclusion, berberine showed a dramatic effect of lowering blood cholesterol and triacylglycerols and improved moderately glucose homeostasis in STZ-induced diabetic rats in association with multiple factors related to insulin resistance.

Recombinant Adeno-Associated Virus-Mediated In Utero Gene Transfer Gives Therapeutic Transgene Expression in the Sheep

Abstract: Somatic in utero gene therapy aims to treat congenital diseases where pathology develops in perinatal life, thereby preventing permanent damage. The aim of this study was to determine whether delivery of self-complementary (sc) adeno-associated virus (AAV) vector in utero would provide therapeutic long-term transgene expression in a large animal model. We performed ultrasound-guided intraperitoneal injection of scAAV2/8-LP1-human Factor IX (hFIX)co (1 × 1012 vector genomes/kg) in early (n = 4) or late (n = 2) gestation fetal sheep. The highest mean hFIX levels were detected 3 weeks after injection in late gestation (2,055 and 1,687.5 ng/ml, n = 2) and 3 days after injection in early gestation (435 ng/ml, n = 1). Plasma hFIX levels then dropped as fetal liver and lamb weights increased, although low levels were detected 6 months after late gestation injection (75 and 52.5 ng/ml, n = 2). The highest vector levels were detected in the fetal liver and other peritoneal organs; no vector was present in...

Hepatotoxicity of kaurene glycosides from Xanthium strumarium L. fruits in mice.

Abstract: The fruit of Xanthium strumarium L. (Cang-Er-Zi) is a traditional Chinese medicine that is used in curing nasal diseases and headache according to the Chinese Pharmacopoeia. However, clinical utilization of Xanthium strumarium is relatively limited because of its toxicity. The present investigation was carried out to evaluate the toxic effects on acute liver injury in mice of the two kaurene glycosides (atractyloside and carbxyatractyloside), which are main toxic constituents isolated from Fructus Xanthii on acute liver injury in mice. Histopathological examinations revealed that there were not obviously visible injury in lungs, heart, spleen, and the central nervous system in the mice by intraperitoneal injection of atractyloside (ATR, at the doses 50,125 and 200 mg/kg) and carbxyatractyloside (CATR, at the doses 50,100 and 150 mg/kg) for 5 days. However, it revealed extensive liver injuries compared with the normal group. In the determination of enzyme levels in serum, intraperitoneal injection of ATR and CATR resulted in significantly elevated serum alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP) activities compared to controls. In the hepatic oxidative stress level, antioxidant-related enzyme activity assays showed that ATR and CATR administration significantly increased hepatic malondialdehyde (MDA) concentration, as well as decreased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) concentration, and this was in good agreement with the results of serum aminotransferase activity and histopathological examinations. Taken together, our results demonstrate that kaurene glycosides induce hepatotoxicity in mice by way of its induction of oxidative stress as lipid peroxidation in liver, which merited further studies. Therefore, these toxic constituents explain, at least in part, the hepatotoxicity of X. strumarium L. in traditional medicine.

Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice.

Abstract: Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF) is obligatory for blastocyst implantation in mice and associated with infertility in women. We aimed to determine whether a PEGylated LIF inhibitor (PEGLA) was an effective contraceptive following vaginal delivery and to identify non-uterine targets of PEGLA in mice. Vaginally-applied 125I-PEGLA accumulated in blood more slowly (30 min vs 10 min) and showed reduced tissue and blood retention (24 h vs 96 h) compared to intraperitoneal injection in mice. Vaginally-applied PEGLA blocked implantation. PEGLA administered by intraperitoneal injection inhibited bone remodelling whereas vaginally-applied PEGLA had no effect on bone. Further, PEGLA had no effect in an animal model of multiple sclerosis, experimental auto-immune encephalomyelitis, suggesting PEGLA cannot target the central nervous system. Vaginally-administered PEGLA is a promising non-hormonal contraceptive, one which could be delivered alone, or in tandem with a microbicide. Vaginal application reduced the total dose of PEGLA required to block implantation and eliminated the systemic effect on bone, showing the vagina is a promising site of administration for larger drugs which target organs within the reproductive tract.

Anti-tumour effects of Egyptian propolis on Ehrlich ascites carcinoma.

Abstract: A total of 150 female Swiss mice were used to study the ability of water soluble propolis derivatives (WSPD) of Egyptian propolis to inhibit the proliferation and growth of Ehrlich ascites carcinoma (EAC) cells in mice. The mice were divided equally into three groups: the first was kept as a negative control group, the second received an intraperitoneal injection of 2.5 × 10(6) EAC and was kept as a positive control group and the third an intraperitoneal injection of 2.5 × 10(6) EAC and treated with propolis (50 mg/kg body weight) administered by gastric intubations 2 h prior to the intraperitoneal injection of EAC. The propolis was administered daily for 11 successive days. An examination of EAC cells revealed a reduction in the volume, total cell count, viable percentage and increase in the percentage of dead cells in the treated group with an increasing mean survival time (MST), increasing life span (ILS) percentage and treated vs positive control (T/C) percentage. Immunological studies revealed a significant increase in the lymphocyte transformation rate (LTR), phagocytic activity and killing power in the group treated with propolis. A haematological study of the parameters revealed leucocytosis in cancer-bearing mice and propolis-treated groups with granulocytosis and monocytosis. The erythrogram revealed a significant reduction in red blood cell (RBC) count in group 2. The result showed that the implantation of EAC in Swiss mice without treatment resulted in a significant decrease in total protein and albumin levels without a change in globulin level and a significant increase in creatinine level, while the third group that received propolis showed an improvement in these biochemical parameters compared to the normal control group.

Intracranial Implantation with Subsequent 3D In Vivo Bioluminescent Imaging of Murine Gliomas

Abstract: The mouse glioma 261 (GL261) is recognized as an in vivo model system that recapitulates many of the features of human glioblastoma multiforme (GBM). The cell line was originally induced by intracranial injection of 3-methyl-cholantrene into a C57BL/6 syngeneic mouse strain (1); therefore, immunologically competent C57BL/6 mice can be used. While we use GL261, the following protocol can be used for the implantation and monitoring of any intracranial mouse tumor model. GL261 cells were engineered to stably express firefly luciferase (GL261-luc). We also created the brighter GL261-luc2 cell line by stable transfection of the luc2 gene expressed from the CMV promoter. C57BL/6-cBrd/cBrd/Cr mice (albino variant of C57BL/6) from the National Cancer Institute, Frederick, MD were used to eliminate the light attenuation caused by black skin and fur. With the use of albino C57BL/6 mice; in vivo imaging using the IVIS Spectrum in vivo imaging system is possible from the day of implantation (Caliper Life Sciences, Hopkinton, MA). The GL261-luc and GL261-luc2 cell lines showed the same in vivo behavior as the parental GL261 cells. Some of the shared histological features present in human GBMs and this mouse model include: tumor necrosis, pseudopalisades, neovascularization, invasion, hypercellularity, and inflammation (1). Prior to implantation animals were anesthetized by an intraperitoneal injection of ketamine (50 mg/kg), xylazine (5 mg/kg) and buprenorphine (0.05 mg/kg), placed in a stereotactic apparatus and an incision was made with a scalpel over the cranial midline. A burrhole was made 0.1 mm posterior to the bregma and 2.3mm to the right of the midline. A needle was inserted to a depth of 3mm and withdrawn 0.4 mm to a depth of 2.6 mm. Two μl of GL261-luc or GL261-luc2 cells (10(7) cells/ml) were infused over the course of 3 minutes. The burrhole was closed with bonewax and the incision was sutured. Following stereotactic implantation the bioluminescent cells are detectable from the day of implantation and the tumor can be analyzed using the 3D image reconstruction feature of the IVIS Spectrum instrument. Animals receive a subcutaneous injection of 150 μg luciferin /kg body weight 20 min prior to imaging. Tumor burden is quantified using mean tumor bioluminescence over time. Tumor-bearing mice were observed daily to assess morbidity and were euthanized when one or more of the following symptoms are present: lethargy, failure to ambulate, hunched posture, failure to groom, anorexia resulting in >10% loss of weight. Tumors were evident in all of the animals on necropsy.

Adriamycin-related anxiety-like behavior, brain oxidative stress and myelotoxicity in male Wistar rats.

Abstract: Chemotherapeutic regimens have been indicated to negatively impact the quality of life for patients. Adriamycin (ADR) is an effective chemotherapeutic agent widely employed for the treatment of human's malignancies; however, it may cause serious side effects. The present study was aimed at investigating the effects of acute administration of ADR on cognitive alterations, brain oxidative status and immune dysregulation in male Wistar rats. Treated animals received a single intraperitoneal injection of ADR (7 mg/kg). Control ones received physiological saline only. Behavioral effects were tested in the elevated plus-maze and the open field which showed that drug-treated rats displayed anxious behavior and deteriorations in the locomotive and exploratory activities over the 72 h following ADR injection as compared to controls. Assessment of brain antioxidant capacity in ADR-injected animals revealed an increase in glutathione-S-transferase activities and malondialdehyde levels while a decrease in glutathione concentrations when compared with the vehicle-treated group. Our results indicated that ADR administration decreased total leukocyte, lymphocyte and granulocyte counts, while enhanced monocyte levels. Moreover, white blood cells (WBC) relative counts in ADR-treated rats showed a significant increase in monocytes and granulocytes and a decrease in lymphocytes as compared to controls. This study suggests that ADR-related cognitive impairments are associated with brain oxidative stress and myelosuppression.

The distribution of salicylate in mouse tissues after intraperitoneal injection.

Abstract: The concentrations of salicylate and its principal metabolites were measured in blood, liver, brain, kidney, heart, spleen, diaphragm and skeletal muscle after the intraperitoneal injection of a fixed amount of radioactive salicylate and varying doses of unlabelled salicylate. The patterns of distribution of salicylate in the various organs with time were similar, the peak level being attained in 30–60 min after injection. Salicylate was eliminated from the blood after 8 hr but persisted in liver in measurable amounts up to 24 hr.

Protective effect of ellagic acid and pumpkin seed oil against methotrexate-induced small intestine damage in rats

Abstract: Gastrointestinal toxicity is one of the most serious side effects in the methotrexate (MTX) treatment. This study was designed to investigate whether ellagic acid (EA) and/or pumpkin seed oil (PSO) had a protective effect on MTX-induced small intestine damage. Forty albino rats were randomized into five groups of 8 rats each. Group I served as a normal control group. In Group II, MTX was administered as a single dose (20 mg/kg) intraperitoneally. Groups III, IV and V were pre-treated respectively with either PSO (40 mg/kg), EA (10 mg/kg) or 0.2% DMSO (vehicle control) orally every day by gavage for 5 days and then they received MTX. All animals were sacrificed 5 days after the intraperitoneal injection of MTX for histopathological examination, estimation of serum prostaglandin E2 (PGE2) level, assay of tissue malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels and myloperoxidase (MPO), xanthine oxidase (XO) and adenosine deaminase (AD) activities. Administration of EA and/or PSO decreased the intestinal damage, PGE2, MDA and NO levels and MPO, XO and AD activities and increased GSH level. These results suggest that EA and PSO protect the small intestine of rats from MTX-induced damage through their antioxidant and anti-inflammatory effects and thus have potential as a promising drug in the prevention of undesired side effects of MTX.

Embryo implantation is blocked by intraperitoneal injection with anti-LIF antibody in mice.

Abstract: Leukemia inhibitory factor (LIF) is essential for embryo implantation in mice and plays an important role in other mammals including humans. Intraperitoneal (i.p.) injections with anti-LIF antibody (7.5 µg/g body weight, 3 times) between D3 (D1 = day of vaginal plug detection) and D4 effectively blocked embryo implantation; complete inhibition was achieved in C57BL/6J mice, and implantation was dramatically reduced in ICR mice (reduced to 27%). Normal rabbit IgG used as the control did not disturb embryo implantation. Anti-LIF antibody was localized not only in the stroma, but also in the luminal epithelium and the glandular lumen after i.p. injections. Growth-arrested blastocysts were recovered from the uterus without any implantation sites in both strains. Blastocysts made contact with the LE on the antimesometrial side; however, uterine stromal cells did not undergo secondary decidual reaction, and the uterine lumen was open, even at D7. Several regions of decidualization in ICR mice treated with anti-LIF antibody were smaller than those of the control, and development of blastocysts was delayed. The expression of LIF-regulated genes, such as immune-responsive gene-1 and insulin-like growth factor binding protein-3, was significantly decreased in C57BL/6J mice treated with anti-LIF antibody compared with the control, but not in ICR mice. The present study demonstrated that simple ip injections of an antibody are sufficient to block one of the important factors involved in embryo implantation in mice, and this method should also be easily applicable to the investigation of other factors involved in implantation.

Evaluation of Mouse Tail-Vein Injections Both Qualitatively and Quantitatively on Small-Animal PET Tail Scans

Abstract: Quantitative small-animal PET of mice requires successful delivery of radiotracers into the venous system. Intravenous injection of radiotracers via lateral tail veins is the most commonly used method of administration and can be technically challenging. Evaluation of the quality of an intravenous injection is necessary to determine whether small-animal PET is quantitatively accurate. The purpose of this study was to evaluate and compare the quality of 50 consecutive intravenous injections into mouse tail veins using both quantitative and qualitative methods. Methods: During 18 F-FDG intravenous injection, qualitative assessment of the injection was performed and classified according to specific criteria as good, intermediate, or poor. Small-animal PET scans of the body and tail were acquired, and tail injection sites were quantitatively assessed in terms of percentage injected dose per gram and classified as low, medium, or high uptake of 18 F-FDG. Qualitative and quantitative methods were compared. To assess baseline amounts of 18FFDG in the tail without a tail injection, 3 additional mice were injected by the intraperitoneal method, imaged, and quantitatively assessed in the same manner. The in vivo imaging data were validated on 7 additional mice by sacrificing them after scans, removing their tails, rescanning the tails, and then measuring the tail radioactivity ex vivo in a g-counter and correlating it with the in vivo amount. Results: Validation of in vivo imaging to ex vivo data yielded an excellent correlation, with an r 2 value of 0.95. Comparison of qualitative and quantitative methods yielded 45 matching results (42 good and low, 2 intermediate and medium, and 1 poor and high). There were 5 cases of mismatching results (1 false-negative and 4 false-positive) between qualitative and quantitative methods. Low-uptake tail injections were comparable to the intraperitoneal injection values. Using qualitative methods, accuracy was true 90% (45/50) of the time. The overall rate of successful intravenous injections was 92% (46/50) using quantitative methods. Conclusion: Qualitative assessment is all that is necessary if the intravenous injection is classified as good. In intermediate, poor, or uncertain classifications, a scan of the tail should be performed for quantitative assessment.

Radon Inhalation Protects Mice from Carbon-Tetrachloride-Induced Hepatic and Renal Damage

Abstract: We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl4-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.