Intraperitoneal Injection (intraperitoneal + injection)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Intraperitoneal Injection

  • daily intraperitoneal injection
  • single intraperitoneal injection

  • Selected Abstracts

    Development of Amygdaloid Kindling in Histidine Decarboxylase,deficient and Histamine H1 Receptor,deficient Mice

    EPILEPSIA, Issue 4 2004
    Tadashi Hirai
    Summary: Purpose: This study attempted to clarify the role of histamine or histamine H1 receptors in the development of amygdaloid kindling by using histidine decarboxylase (HDC)-deficient and histamine H1 receptor (H1R)-deficient mice. Methods: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. A bipolar electroencephalogram was recorded; bipolar stimulation of the amygdala was applied every day with a constant-current stimulator and continued until a generalized convulsion was obtained. Results: The development of amygdaloid kindling in HDC-deficient and H1R-deficient mice was significantly accelerated compared with that in their respective wild-type mice. In addition, the afterdischarge (AD) duration and generalized seizure duration in HDC-deficient and H1R-deficient mice were prolonged. Intraperitoneal injection of histidine resulted in an inhibition of amygdaloid kindled seizures in wild-type mice at doses that caused an increase in the histamine contents of the brain. However, no significant effect was observed with histidine in H1R-deficient mice at the same dose. Conclusions: These findings suggest that histaminergic mechanisms through H1 receptors play a crucial role not only in amygdaloid kindled seizures but also in the development of amygdaloid kindling. [source]

    Type II collagen without adjuvant induces eosinophilic arthritis

    Robert Bockermann
    Abstract Eosinophilia is a characteristic feature of many inflammatory diseases including inflammatory bowel disease and asthma. It also occurs in a subtype of rheumatoid arthritis but the role of eosinophils has been unclear and animal models have been lacking. Here, we introduce a new mouse model to study the role of eosinophilia in arthritis. Intraperitoneal injection of type II collagen alone, without any adjuvant, was sufficient to induce chronic arthritis in a mouse with transgenic T cells specific for type II collagen. The arthritis was accompanied by infiltration of eosinophils into the synovial tissue and the disease could be blocked with neutralizing anti-IL-5 antibodies. To our knowledge, this is the first description of an eosinophilic disease form of destructive arthritis. [source]

    ORIGINAL ARTICLE: The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intake

    J.-Y. Sun
    Summary The aim of this study was to investigate the anorectic mechanism of calcitonin gene-related peptide (CGRP) in rats. Intraperitoneal injection of CGRP (50 ,g/kg) resulted in decline (p < 0.05) in the food intake of rats at 0.5, 1, 2 and 4 h in comparison with saline control. Compared with saline-treated group, the levels of hypothalamic 3,,5,-cyclic adenosine monophosphate (cAMP) and plasma glucagon were increased (p < 0.05) in CGRP-treated group, but insulin level was decreased (p < 0.05). No significant changes (p > 0.05) in the plasma leptin were observed between two treatment groups. Calcitonin gene-related peptide injection down regulated (p < 0.05) both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) genes at mRNA levels, but up regulated (p < 0.05) the expression of cholecystokinin (CCK) gene. The correlations analysis showed that food intake was negatively correlated (p < 0.05) with CCK mRNA, cAMP and glucagon levels. Moreover, there existed negative correlations (p < 0.05) between MCH mRNA and glucagon levels, and positive correlations (p < 0.05) between insulin and leptin levels. The results showed that cAMP acting as the second messenger may play a vital role in the anorectic effects of CGRP. Calcitonin gene-related peptide could stimulate anorexigenic neuropeptides (i.e. CCK) and/or inhibit orexigenic neuropeptides (i.e. NPY and MCH) expression, and ultimately suppressed food intake that was functionally coupled to cAMP/PKA pathway activation. [source]

    Intraperitoneal injection of d- galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver

    Yoshiji Asaoka
    Abstract In an in vivo 5-week initiation assay model, chemical hepatectomy by hepatotoxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of d- galactosamine (d -gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of d -gal (700 mg kg,1, i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d -gal (i.p.) the BrdU index was markedly elevated (27.5% ± 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d -gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using d -gal i.p. is high, so that d -gal i.p. can be considered an effective cell proliferation stimulus. Copyright © 2005 John Wiley & Sons, Ltd. [source]

    Involvement of , protein kinase C in estrogen-induced neuroprotection against focal brain ischemia through G protein-coupled estrogen receptor

    Shigeto Hayashi
    Abstract The neuroprotective effects of estrogen were studied in the ischemic model mice by 90 min transient unilateral middle cerebral artery occlusion (MCAO) followed by 22.5 h reperfusion. The total infarct size in C57BL/6 female mice after MCAO and reperfusion was significantly smaller than that in male mice. Intraperitoneal injection of estrogen after the start of reperfusion significantly reduced the infarct volume in the male mice. However, no significant gender difference was found in total infarct size in , protein kinase C (PKC)-knockout mice, suggesting that the neuroprotective effects of estrogen are due to the activation of a specific subtype of PKC, ,PKC, a neuron-specific PKC subtype, in the brain. We demonstrated that exogenous estrogen-induced neuroprotection was attenuated in ,PKC-knockout mice. Immunocytochemical study showed that ,PKC was translocated to nerve fiber-like structures when observed shortly after MCAO and reperfusion. We also visualized the rapid and reversible translocation of ,PKC-GFP (green fluorescent protein) by estrogen stimulation in living CHO-K1 cells. These results suggest that the activation of ,PKC through the G-protein-coupled estrogen receptors on the plasma membrane is involved in the estrogen-induced neuroprotection against focal brain ischemia. [source]

    Thyroid hormone stimulates ,-glutamyl transpeptidase in the developing rat cerebra and in astroglial cultures

    Asmita Dasgupta
    Abstract Hypothyroidism in the developing rat brain is associated with enhanced oxidative stress, one of the earliest manifestations of which is a decline in the level of glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH homeostasis, the effect of TH on ,-glutamyl transpeptidase (,GT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral ,GT at all postnatal ages examined (postnatal day 1,20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal injection of TH to 15-day-old rat pups increased the specific activity of ,GT by 25-30% within 4,6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of ,GT by 30,40% within 4,6 hr. The induction of ,GT by TH was blocked by actinomycin D or cycloheximide. ,GT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the ,GT-inhibitor, acivicin, GSH released in the culture medium of astrocytes increased linearly for at least 6 hr and TH had no effect on this accumulation pattern. In the absence of acivicin, GSH content of the medium from TH-treated cells was significantly lower than that of untreated controls due to activation of ,GT by TH and a faster processing of GSH. Because the products of ,GT reaction are putative precursors for neuronal GSH, the activation of ,GT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress. © 2005 Wiley-Liss, Inc. [source]

    Antinociceptive properties of coumarins, steroid and dihydrostyryl-2-pyrones from Polygala sabulosa (Polygalaceae) in mice

    Juliana V. Ardenghi
    We have investigated the possible antinociceptive action of the extract, fractions and pure compounds obtained from the whole plant Polygala sabulosa A. W. Bennett (Polygalaceae) in acetic acid-induced visceral pain in mice. Intraperitoneal injection of animals with the hydroalcoholic extract and fractions (CH2Cl2, EtOAc, n -BuOH, aqueous fraction) (1,100 mg kg,1) caused a dose-related and significant inhibition of the acetic acid-induced visceral nociceptive response. The CH2Cl2, EtOAc and n -BuOH fractions were more potent than the hydroalcoholic extract and aqueous fraction. The isolated compounds dihydrostyryl-2-pyrones (1, 2, 3), styryl-2-pyrone (7), ,-spinasterol (9), scopoletin (10) and two esters of the coumarin (scopoletin) obtained semisynthetically, acetylscopoletin (10a) and benzoylscopoletin (10b) (0.001,10 mg kg,1), exhibited significant and dose-related antinociceptive effects against acetic acid-induced visceral pain. The results distinguished, for the first time, the extract, fractions and pure compounds obtained from P. sabulosa that produced marked antinociception against the acetic acid-induced visceral nociceptive response, supporting the ethnomedical use of P. sabulosa. [source]

    Enhancement of natural killer cell activity of aged mice by modified arabinoxylan rice bran (MGN-3/Biobran)

    Mamdooh Ghoneum
    The present study is aimed to examine the possibility of enhancement of natural killer (NK) cell activity in aged C57BL/6 and C3H mice using MGN-3, a modified arabinoxylan from rice bran. Intraperitoneal injection of MGN-3 (10 mg kg,1 per day) caused a remarkable increase in the peritoneal NK activity as early as 2 days (35.2 lytic units), and the level remained elevated through day 14. The control aged mice had a level of 5.8 lytic units. Enhancement in NK activity was associated with an increase in both the binding capacity of NK cells to tumour targets and in the granular content as measured by BLT-esterase activity. Treatment did not alter the percentage of peritoneal NK cells. Data showed that peritoneal macrophages inhibit NK activity. In conclusion, MGN-3 enhances murine NK activity of aged mice and may be useful for enhancing NK function in aged humans. [source]

    6-Formylpterin protects retinal neurons from transient ischemia,reperfusion injury in rats: A morphological and immunohistochemical study

    NEUROPATHOLOGY, Issue 3 2003
    Taisaku Funakoshi
    Neuroprotective effects of 6-formylpterin (6FP) on transient retinal ischemia,reperfusion injury were evaluated in rats by means of counting the number of retinal ganglion cells, measuring the thicknesses of the inner plexiform and inner nuclear layers, and by immunohistochemical detection of apoptotic cells in the retina. Sixty-one Sprague,Dawley rats (12 weeks, male, 295,330 g) were subjected to transient retinal ischemia,reperfusion by elevated intra-ocular pressure (80 mmHg for 60 min). Intraperitoneal injection of 6FP (3.8 mg/kg) was performed before or after ischemia. The retina was histologically better preserved in rats with 6FP treatment than without 6FP treatment. 6FP showed more strong neuroprotective effects when it was administered before ischemia. The number of single-stranded DNA-positive cells in the retina also decreased remarkably in rats with 6FP treatment, especially when administered before ischemia. These results suggest that 6FP protects retinal neurons from transient ischemia,reperfusion injury, at least in part by inhibiting apoptotic cell death. [source]

    CpG-containing ODN has a limited role in the protection against Toxoplasma gondii

    R. Saavedra
    SUMMARY Bacterial DNA containing immunostimulatory motifs (CpG) induces the development of a TH1 immune response. Since protection against Toxoplasma gondii is correlated with this type of response, the aim of this work was to determine if a synthetic oligodeoxynucleotide (ODN) containing CpG sequences could be useful as adjuvant for the induction of a long-lasting protective immune response against T. gondii. BALB/c mice immunized with a total soluble antigen of T. gondii (TSA2) mixed with ODN-containing CpG sequences developed a typical TH1 response, as determined by antibody isotypes and interferon-, (IFN-,) and interleukin-4 (IL-4) production by spleen cells. However, they did not resist a challenge with the virulent RH strain of the parasite. Absence of protection paralleled with lower levels of IFN-,, when compared with mice vaccinated with the live tachyzoites of the attenuated ts.4 strain of the parasite, which resisted this challenge. Intraperitoneal injection of ODN alone to mice induced a high degree of resistance to a lethal challenge inoculated by the same route. Nevertheless, this nonspecific protection was transient. Thus, the use of ODN containing CpG motifs as adjuvant is of limited value for the induction of a protective immune response against T. gondii. [source]

    Intracerebroventricular Effects of Histaminergic Agents on Morphine-Induced Anxiolysis in the Elevated Plus-Maze in Rats

    Mohammad-Reza Zarrindast
    It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine-induced anxiolysis in rats, using elevated plus-maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 ,g/rat) also increased anxiety-related behaviours. Intracerebroventricular injection of pyrilamine, a H1 receptor antagonist (25, 50 and 100 ,g/rat), increased anxiety whereas injection of ranitidine, a H2 receptor antagonist (5, 10 and 20 ,g/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H2 receptors, while the response of H1 blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 ,g/rat), pyrilamine (50 ,g/rat) and ranitidine (5 ,g/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 ,g/rat), pyrilamine (25, 50 and 100 ,g/rat) or ranitidine (5, 10 and 20 ,g/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety-related indices in the elevated plus-maze. This may imply that morphine-induced anxiolysis probably is independent of the histaminergic system. [source]

    GABA Mechanisms and Antinociception in Mice with Ligated Sciatic Nerve

    Mohammad-Reza Zarrindast
    The response to morphine or GABA receptor agonists was examined 14 days after unilateral nerve ligation by hot-plate test. Intraperitoneal injection of different doses of morphine (3, 6 and 9 mg/kg), muscimol (0.5, 1 and 2 mg/kg) or baclofen (1, 2.5 and 5 mg/kg) induced a dose-related antinociception in both intact and ligated mice. The response of morphine but not that of muscimol or baclofen, in nerve-ligated mice was significantly less than that induced in the intact animals. The responses induced by muscimol or baclofen in nerve-ligated animals, were reduced by bicuculline or CGP35348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid], respectively. However, morphine in combination with muscimol (2 mg/kg) tends to induce higher response; the combination of the GABA receptor agonists with morphine did not show potentiation, but additive effect. The opioid receptor antagonist naloxone reduced the response induced by muscimol in nerve-ligated animals. It was concluded that although ligation of the sciatic nerve clearly reduced the analgesic effect of morphine and not that of the GABA agonists, the results nevertheless indicated that morphine and the GABAA agonist shared the same mechanism of action. [source]

    Anti-sickling effect of MX-1520, a prodrug of vanillin: an in vivo study using rodents

    Chaojie Zhang
    Summary Vanillin, a food additive, covalently binds with sickle haemoglobin (Hb S), inhibits cell sickling and shifts the oxygen equilibrium curve towards the left. These effects would potentially benefit patients with sickle cell disease (SCD). However, vanillin has no therapeutic effect if given orally because orally administered vanillin is rapidly decomposed in the upper digestive tract. To overcome this problem, a vanillin prodrug, MX-1520, which is biotransformed to vanillin in vivo, was synthesized. Studies using transgenic sickle mice, which nearly exclusively develop pulmonary sequestration upon exposure to hypoxia, showed that oral administration of MX-1520 prior to hypoxia exposure significantly reduced the percentage of sickled cells in the blood. The survival time under severe hypoxic conditions was prolonged from 6·6 ± 0·8 min in untreated animals to 28·8 ± 12 min (P < 0·05) and 31 ± 7·5 min (P < 0·05) for doses of 137·5 and 275 mg/kg respectively. Intraperitoneal injection of MX-1520 to bypass possible degradation in the digestive tract showed that doses as low as 7 mg/kg prolonged the survival time and reduced the percentage of sickled cells during hypoxia exposure. These results demonstrate the potential for MX-1520 to be a new and safe anti-sickling agent for patients with SCD. [source]

    Hypocretin-1 Dose-Dependently Modulates Maternal Behaviour in Mice

    K. L. D'Anna
    Increases in neuronal activity of hypocretin (HCRT), a peptide involved in arousal, and in HCRT-1 receptor mRNA expression have recently been identified in association with lactation. HCRT is released within brain regions regulating maternal behaviour and it is possible that increased HCRT neurotransmission during lactation supports maternal care. The present study examined for the first time the behavioural effects of HCRT on lactating mice. At intermediate doses, intracerebroventricular (i.c.v.) injections of HCRT-1 (0.06 and 0.1 µg) elevated levels of licking and grooming of pups (but not self-grooming) and number of nursing bouts without affecting other behaviours. At the highest dose, HCRT-1 (0.3 µg, i.c.v) delayed latency to nurse, decreased nursing, increased time off nest, and decreased maternal aggression. Intraperitoneal injections of the HCRT-1 receptor antagonist, SB-334867, exhibited a general trend towards increasing time spent low-arched back nursing (P = 0.053) and decreasing licking and grooming of pups while high-arched back nursing (P = 0.052). This suggests that the endogenous release of HCRT, working independently or dependently with other neuromodulators, may be necessary for full maternal behaviour expression. Possible sites of HCRT action in enhancing and impairing maternal care were identified via examinations of c,Fos immunoreactivity in association with i.c.v. HCRT injections. Together, these finding support the idea of HCRT modulating maternal behaviour, with intermediate levels (0.06 and 0.1 µg) supporting (even augmenting) some behaviours, but with levels that are too high (0.3 µg HCRT, i.c.v.), maternal behaviour and aggression are suppressed. [source]

    Effect of Naloxone on Appetitive and Consummatory Phases of Ethanol Self-Administration

    ALCOHOLISM, Issue 7 2001
    Amanda L. Sharpe
    Background : The opioid system has been implicated in ethanol self-administration. Morphine, an opiate agonist, can sometimes increase the amount of ethanol consumed, and opiate antagonists such as naloxone and naltrexone decrease the amount of ethanol consumed in both animals and humans. The objective of this study was to examine the effect of naloxone on appetitive (or seeking) and consummatory behaviors by using an operant model developed to separate these two phases of self-administration. Methods: Intraperitoneal injections of naloxone (0.3,10 mg/kg) or vehicle were given before operant self-administration sessions to assess the effect on lever pressing (appetitive behavior) and subsequent consumption. Effects were measured in two groups of rats: one self-administered a 3% sucrose solution and the other a 10% ethanol solution. Results: Naloxone dose-dependently decreased ethanol and sucrose consumption by an earlier cessation of drinking in the session compared with vehicle injection days. There were some effects on appetitive responding after treatment with naloxone, but none was statistically significant. Conclusions: Naloxone may decrease ethanol self-administration by decreasing the postingestive or pharmacological effects of alcohol. This model provides a new method for examining the effects of potential pharmacotherapeutics on alcohol self-administration behavior. [source]

    Alpha-melanocyte-stimulating hormone attenuates behavioral effects of corticotropin-releasing factor in isolated guinea pig pups

    Patricia A. Schiml-Webb
    Abstract During a 3-hr period of social isolation in a novel environment, guinea pig pups exhibit an initial active phase of behavioral responsiveness, characterized primarily by vocalizing, which is then followed by a stage of passive responsiveness in which pups display a distinctive crouch, eye-closing, and extensive piloerection. Prior treatment of pups with alpha-melanocyte-stimulating hormone (,-MSH) reduces each of the passive behaviors. The onset of passive responding during separation can be accelerated with peripheral injection of corticotropin-releasing factor (CRF). To examine whether CRF produces its effects through a mechanism similar to that of prolonged separation, we examined the effect of administering ,-MSH to pups injected with CRF. As expected, CRF markedly enhanced passive responding during a 60-min period of separation. ,-MSH delivered by either intracerebroventricular infusion or intraperitoneal injection significantly reduced each of the passive behavioral responses without significantly affecting active behavior. These findings, together with previous results indicating that it is the anti-inflammatory property of ,-MSH that is responsible for its behavioral effects during prolonged separation, suggest that peripheral CRF speeds the induction of passive responding through a mechanism involving enhanced proinflammatory activity. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 399,407, 2009. [source]

    No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days,,

    Kristine L. Witt
    Abstract Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282,1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats. Environ. Mol. Mutagen. 2010. Published 2009 Wiley-Liss, Inc. [source]

    Molecular cloning of CYP1A gene and its expression by benzo(a)pyrene from goldfish (Carassius auratus)

    Seung-Min Oh
    Abstract We cloned and sequenced the cytochrome P450 1A (CYP1A) gene from goldfish (Carassius auratus). It has a 1581 bp open reading frame that encodes a 526 amino acid protein with a theoretical molecular weight of 59.02 kDa. The CYP1A amino acid sequence clusters in a monophyletic group with other fish CYP1As, and more closely related to zebrafish CYP1A (91% identity) than to other fish CYP1As. Exposure to benzo(a)pyrene (BaP) by intraperitoneal injection increased biliary BaP metabolites and liver CYP1A gene expression. BaP exposure also increased CYP1A gene expression in extrahepatic organs, including intestine, and gill, which are sensitive to aqueous and dietary exposure to Arylhydrocarbon receptor (AhR) agonists. Therefore, goldfish CYP1A identified in this study offers basic information for further research related to biomarker use of CYP1A of goldfish. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source]

    Effect of di(n -butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid rats

    Ena Lee
    Abstract This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 ,g/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor ,-1 (TR,-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 245,255, 2007. [source]

    Toxicology of a Microcystis ichthyoblabe waterbloom from Lake Oued Mellah (Morocco)

    Brahim Sabour
    Abstract In the Lake Oued Mellah cyanobacteria waterblooms occur periodically in late spring and summer with Microcystis ichthyoblabe as the main bloom-forming species. In 1999, a heavy waterbloom of M. ichthyoblabe occurred during May June with a maximal biomass of 298 mg/l. During this period, several bloom samples were collected. The toxicity assessment was done by mouse and brine shrimp (Artemia) bioassays. Apart from the sample collected on 15/06/1999, all the other samples were toxic by mouse bioassay. The LD50 determined by intraperitoneal injection to mice during active cyanobacterial growth and decline phases were 518 and 1924 mgDW/kg respectively. Using Artemia bioassay, the 24hLC50 varied from 6.0 to 40.6 mg/ml and the 48hLC50 ranged from 2.8 to 18.2 mg/ml. The separation and identification of microcystin variants was performed by high performance liquid chromatography,photodiode array detection. Eleven toxins were separated and preliminarily identified as microcystin variants as they exhibit a typical UV spectra like the microcystin-LR standard. The quantification of total microcystins determined by enzyme-linked immunosorbent assay showed that the contents were varied between 0.1 and 0.76 ,g/g DW. © 2002 by Wiley Periodicals, Inc. Environ Toxicol 17: 24,31, 2002 [source]

    Lead accumulation in feathers of nestling black-crowned night herons (Nycticorax nycticorax) experimentally treated in the field

    Nancy H. Golden
    Abstract Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate noninvasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four- to 6-d-old heron nestlings (one/nest) at Chincoteague Bay, Virginia (USA), received a single intraperitoneal injection of dosing vehicle (control, n = 7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body wt of nestling; n = 6 or 7/dose) chosen to yield feather lead concentrations found at low- to moderately polluted sites. Nestlings were euthanized at 15 d of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32,0.74, p < 0.02) but exhibited only modest dose dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds. [source]

    Pentylenetetrazol-induced Recurrent Seizures in Rat Pups: Time Course on Spatial Learning and Long-term Effects

    EPILEPSIA, Issue 6 2002
    Li-Tung Huang
    Summary: ,Purpose: Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood. Methods: Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus. Results: PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone. Conclusions: Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence. [source]

    Nod1 and Nod2 induce CCL5/RANTES through the NF-,B pathway

    Catherine Werts
    Abstract The Nod-like receptor proteins Nod1 and Nod2 participate in innate immune responses against bacteria through intracellular detection of peptidoglycan, a component of bacterial cell wall. Recent evidence has demonstrated that Nod1 stimulates the release of chemokines that attract neutrophils at the site of infection, such as CXCL8/IL-8 in humans, and CXCL1/keratinocyte-derived chemokine and CXCL2/MIP-2 in mice. We aimed to determine whether Nod proteins could trigger the release of CCL5/RANTES, a chemokine known to attract a number of immune cells, but not neutrophils. Our results demonstrate that activation of both Nod1 and Nod2 results in substantial secretion of CCL5 by murine macrophages. Moreover, in vivo, the intraperitoneal injection of murine Nod1 or Nod2 agonists resulted in a rapid secretion of CCL5 into the bloodstream. We also observed that Nod-dependent secretion of CCL5 did not correlate with the induction of the interferon-, pathway, a major signaling cascade for the activation of CCL5 by viruses. In contrast, we identified a key role of the NF-,B pathway in Nod-dependent stimulation of the CCL5 promoter. Together, these results identify a novel target downstream of Nod1 and Nod2, which is likely to play a key role in orchestrating the global Nod-dependent immune defense during bacterial infections. [source]

    PRECLINICAL STUDY: Pentylenetetrazole-induced status epilepticus following training does not impair expression of morphine-induced conditioned place preference

    ADDICTION BIOLOGY, Issue 2 2009
    Jie Zhang
    ABSTRACT Learning and memory play an important role in morphine addiction. Status epilepticus (SE) can impair the spatial and emotional learning and memory. However, little is known about the effects of SE on morphine-induced conditioned place preference (CPP). The present study was designed to investigate the effects of SE on morphine CPP, with food CPP being used as a control. The effects of SE on spatial memory in the Morris water maze (MWM) and Y-maze were investigated. SE was induced in adult mice using intraperitoneal injection of pentylenetetrazole; control mice received saline. The data indicated that SE had no effects on the formation of morphine CPP; however, the formation of food CPP was blocked by SE. Meanwhile, spatial memory assayed in the MWM and Y-maze was impaired by SE. In addition, the data demonstrated that SE did not cause a lasting disturbance of motor activity nor a change in the mice's appetite. These results suggested that although SE had no effects on morphine CPP, there was impaired food CPP and spatial memory in both the MWM and the Y-maze. The mechanisms underlying memory process of morphine CPP may be different from other types of memory. [source]

    Extracellular signal-regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesis

    Solčne Languille
    Abstract The ability to form long-term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny. [source]

    Impact of S100B on local field potential patterns in anesthetized and kainic acid-induced seizure conditions in vivo

    Seiichi Sakatani
    Abstract S100B is a calcium-binding protein predominantly expressed in astrocytes. Previous studies using gene-manipulated animals have suggested that the protein has a role in synaptic plasticity and learning. In order to assess the physiological roles of the protein in active neural circuitry, we recorded spontaneous neural activities from various layers of the neocortex and hippocampus in urethane-anesthetized S100B knockout (KO) and wildtype (WT) control mice. Typical local field oscillation patterns including the slow (0.5,2 Hz) oscillations in the neocortex, theta (3,8 Hz) and sharp wave-associated ripple (120,180 Hz) oscillations in the hippocampus were observed in both genotypes. Comparisons of the frequency, power and peak amplitude have shown that these oscillatory patterns were virtually indistinguishable between WT and KO. When seizure was induced by intraperitoneal injection of kainic acid, a difference between WT and KO appeared in the CA1 radiatum local field potential pattern, where seizure events were characterized by prominent appearance of hyper-synchronous gamma band (30,80 Hz) activity. Although both genotypes developed seizures within 40 min, the gamma amplitude was significantly smaller during the development of seizures in KO mice. Our results suggest that deficiency of S100B does not have a profound impact on spontaneous neural activity in normal conditions. However, when neural activity was sufficiently raised, activation of S100B-related pathways may take effect, resulting in modulation of neural activities. [source]

    Acute and long-term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections

    R. Ferrari
    Abstract We have examined several neurochemical and behavioural parameters related to the function of the mesolimbic dopamine (DA) pathway in animals treated with nicotine following three modes of drug administration, i.e. systemic intraperitoneal injection, intra-accumbens (Acb) infusion or intraventral tegmental area (intra-VTA) microinjection. The present modes of systemic, intra-Acb and intra-VTA nicotine administration elicited comparable acute increases in dialysate DA levels from the Acb. The increase in extracellular DA levels was paralleled by a significant enhancement of locomotion in a habituated environment in the case of systemic or intra-VTA nicotine administration, whereas unilateral or bilateral intra-Acb nicotine infusion was ineffective, showing that accumbal DA increase is not sufficient to elicit locomotion in this experimental paradigm. Intra-VTA, but not systemic or intra-Acb, nicotine administration caused a long-term (at least 24-h) increase in basal dialysate DA levels from the Acb. In addition, significant increases in tyrosine hydroxylase (TH) and GluR1 (but not dopamine transporter or NR1) mRNA levels in the VTA were detected 24 h after intra-VTA nicotine administration. Systemic nicotine injection caused only an increase in TH mRNA levels while intra-Acb infusion did not modify any of the mRNAs tested. The long-term increase in basal DA levels in the Acb and TH, and GluR1 mRNA levels in the VTA upon intra-VTA nicotine microinjection indicates that even a single nicotine injection can induce plastic changes of the mesolimbic DA pathway. [source]

    Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki rat

    F. C. Howarth
    Type 2 diabetes mellitus accounts for more than 90% of all cases of diabetes mellitus, and cardiovascular complications are the major cause of mortality and death in diabetic patients. The chronic effects of type 2 diabetes mellitus on heart function have been investigated in the Goto-Kakizaki (GK) rat. Experiments were performed in GK rats and age-matched Wistar control rats at 18 months of age. The progressive effects of diabetes on glucose metabolism were monitored periodically by application of the glucose tolerance test. Ventricular action potentials were measured in isolated, perfused heart. Shortening and intracellular Ca2+ were measured in electrically stimulated ventricular myocytes. The GK rats displayed mild fasting hyperglycaemia and progressively worsening glucose tolerance. At 18 months of age and 180 min after intraperitoneal injection of glucose (2 g (kg body weight),1), blood glucose was 436 ± 47 mg dl,1 in GK rats compared with 153 ± 18 mg dl,1 in control animals. Heart weight to body weight ratio was significantly increased in GK rats (4.10 ± 0.09 mg g,1, n= 5) compared with control animals (3.36 ± 0.22 mg g,1, n= 4). Spontaneous heart rate was slightly reduced in GK rats compared with control rats. Although the amplitude of shortening was not altered, the amplitude of the Ca2+ transient was significantly increased in myocytes from GK rats (0.78 ± 0.11 ratio units) compared with control rats (0.50 ± 0.06 ratio units). Despite progressively worsening glucose metabolism, at 18 months of age the contractile function of the heart appears to be well preserved. [source]

    The ameliorative effect of cysteine prodrug l -2-oxothiazolidine-4-carboxylic acid on cisplatin-induced nephrotoxicity in rats

    B.H. Ali
    Abstract Pathogenesis of nephrotoxicity of the synthetic anticancer drug cisplatin (CP) involves generation of reactive oxygen species and free radicals in the kidney cortex, and cysteine prodrug l -2-oxothiazolidine-4-carboxylic acid (OTC) has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of OTC on CP nephrotoxicity in rats. OTC was given at an oral dose of 150 mg/kg/day for 7 days. On day 7, some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg. Rats were killed, blood and urine samples were collected, and the kidneys were removed 6 days after CP treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex, and by urinalyses. CP significantly increased the concentrations of urea and creatinine (P < 0.05) by about 128% and 170% respectively. CP treatment reduced cortical GSH concentration by about 34% (P < 0.05), and the activity of SOD by about 28% (P < 0.05). CP treatment significantly increased urine volume and N -acetyl- , - d -glucosaminidase (NAG) activity, and significantly decreased osmolality and protein concentrations. OTC significantly mitigated all these effects. Sections from saline- and OTC-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This appeared to be lessened when CP was given simultaneously with OTC. The concentration of CP in the cortical tissues was not significantly altered by OTC treatment. The results suggested that OTC had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, OTC may potentially be useful as a nephroprotective agent. [source]

    Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain

    Sameer Sharma
    Abstract Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor- , (TNF- ,) and whole brain nitric oxide (NO) release. Four weeks after a single intraperitoneal injection of streptozotocin (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights when compared with control mice. Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF- , levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain. [source]