strychnine and Body-Weight

Plants and herbs have been used by women throughout history for therapeutic purposes. Strychnos pseudoquina, a plant used in the treatment of various diseases, can also function as an abortive herb. There is no scientific confirmation of its effects during pregnancy, and the activity of this plant needs to be substantiated or refuted with experimental evidence.. Evaluating the effect of the S. pseudoquina aqueous extract on maternal reproductive toxicity and fetal development.. The aqueous extract of S. pseudoquina bark was evaluated in Wistar rats. Pregnant rats were distributed into four experimental groups (n = 12 rats/group): Control = treated with water (vehicle); Treated 75, Treated 150, and Treated 300 = treated with S. pseudoquina at dose 75, 150 and 300 mg/kg, respectively. The rats were treated by an intragastric route (gavage) from day 0 to day 21 of pregnancy. At the end of pregnancy, maternal reproductive outcomes, organs, biochemical and hematological profiles, fetuses, and placentas were analyzed. Maternal toxicity was evaluated through body weight gain, water, and food intake. With knowledge of the harmful dosage of the plant, other rats were used on gestational day 4 for the evaluation of morphological analyses before embryo implantation. P < 0.05 was considered as statistically significant.. The S. pseudoquina treatment showed elevated liver enzymatic activities. The Treated 300 group presented toxicity with reduced maternal body weight, water and food intake, and increased kidney relative weight compared to those of the Control group. At a high dosage, the plant presents an abortifacient activity, confirmed by embryo losses before and after implantation and degenerated blastocysts. In addition, the treatment contributed to an increased percentage of fetal visceral anomalies, decreased ossification sites, and intrauterine growth restriction (300 mg/kg dose).. In general, our study showed that an aqueous extract of S. pseudoquina bark caused significant abortifacient activity that testified to its traditional use. Furthermore, the S. pseudoquina extract caused maternal toxicity that contributed to impaired embryofetal development. Therefore, the use of this plant should be completely avoided during pregnancy to prevent unintended abortion and risks to maternal-fetal health.

Topics: Abortifacient Agents; Animals; Body Weight; Female; Plant Extracts; Pregnancy; Rats; Rats, Wistar; Strychnos; Water; Weight Gain

To compare the pharmaceutical properties and the anti-tumor activities of three kinds of stealth liposomes prepared with different phospholipid composition containing brucine.. Stealth liposomes with different phospholipids composition, such as soybean phosphatidycholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC) and the complex of SPC and HSPC, were prepared by ammonium sulfate transmembrane gradient method. Pharmaceutical properties such as shape, encapsulation efficiency and size of three stealth liposomes were compared intensively. Anti-tumor activity of SPC, HSPC and novel stealth liposomes composed of both SPC and HSPC were compared by established mouse liver cancer H22 model. Meanwhile, the mice body weight and immune organ weight were also compared.. The encapsulation efficiency of novel, SPC and HSPC stealth liposomes were 77.7%, 64.8% and 74.8%, respectively. The mean diameters of them were less than 100 nm. The tumor inhibition rate of novel, HSPC and SPC stealth liposomes were 57.88%, 49.15%, 23.37%, respectively. The mice body weight, thymus gland index of three stealth liposomes group and spleen index of novel stealth liposomes group had no significant difference with the negative group while SPC and HSPC stealth liposomes group increased the spleen index.. Phospholipids composition is the key factor which determines the antitumor activity of brucine-loaded stealth liposomes.

Topics: Animals; Antineoplastic Agents; Body Weight; Cell Line, Tumor; Cell Proliferation; Humans; Liposomes; Mice; Particle Size; Phospholipids; Strychnine

Previous work has shown that latent respiratory motor pathways known as crossed phrenic pathways are inhibited via a spinal inhibitory process; however, the underlying mechanisms remain unknown. The present study investigated whether spinal GABA-A and/or glycine receptors are involved in the inhibition of the crossed phrenic pathways after a C2 spinal cord hemisection injury. Under ketamine/xylazine anesthesia, adult, female, Sprague-Dawley rats were hemisected at the C2 spinal cord level. Following 1 week post injury, rats were anesthetized with urethane, vagotomized, paralyzed and ventilated. GABA-A receptor (bicuculline and Gabazine) and glycine receptor (strychnine) antagonists were applied directly to the cervical spinal cord (C3-C7), while bilateral phrenic nerve motor output was recorded. GABA-A receptor antagonists significantly increased peak phrenic amplitude bilaterally and induced crossed phrenic activity in spinal-injured rats. Muscimol, a specific GABA-A receptor agonist, blocked these effects. Glycine receptor antagonists applied directly to the spinal cord had no significant effect on phrenic motor output. These results indicate that phrenic motor neurons are inhibited via a GABA-A mediated receptor mechanism located within the spinal cord to inhibit the expression of crossed phrenic pathways.

Topics: Animals; Bicuculline; Body Weight; Efferent Pathways; Female; GABA Antagonists; gamma-Aminobutyric Acid; Glycine; Glycine Agents; Phrenic Nerve; Pyridazines; Rats; Rats, Sprague-Dawley; Receptors, Glycine; Respiratory Mechanics; Respiratory Muscles; Spinal Cord Injuries; Stereotaxic Techniques; Strychnine; Vagotomy

We tested the hypothesis that respiratory development would be retarded in tadpoles reared in aquaria in which a barrier prevented access to the air-water interface. To test this hypothesis, we examined swimming behavior and respiration in intact tadpoles and gill and lung respiratory activity and central chemosensory responses in an in vitro brainstem preparation. The "barrier" tadpoles had significantly lower resting gill frequencies and higher lung breath attempts than control tadpoles at the same metamorphic stage. Control tadpoles swam greater distances and spent more time in the upper one third of the aquaria, while barrier tadpoles spent significantly more time at the bottom of the aquaria. There was significantly greater mortality for barrier tadpoles compared to control animals in the earliest and latest metamorphic stages. Mean body weight was significantly greater, and metamorphic rate was reduced in barrier tadpoles. Neither control nor barrier tadpole brainstem preparations demonstrated a gill ventilatory response to CO(2); however, both control and barrier preparations possessed significant lung frequency responses to central CO(2) chemoreceptor stimulation. Bath application of the GABA(A) and glycine receptor antagonists, bicuculline and strychnine, had greater effects on control tadpole gill burst activity and produced a similar large-amplitude bursting pattern in both control and barrier tadpoles, that was insensitive to CO(2) chemoreceptor stimulation. We conclude that development of the respiratory pattern was perturbed by the barrier, but the major effect was on gill ventilation rather than lung ventilation as we had expected.

Topics: Animals; Bicuculline; Body Weight; Carbon Dioxide; Chemoreceptor Cells; Feedback, Physiological; Female; GABA-A Receptor Antagonists; Gills; Larva; Lung; Lung Volume Measurements; Male; Metamorphosis, Biological; Neurotransmitter Agents; Pulmonary Ventilation; Rana catesbeiana; Receptors, Glycine; Respiration; Strychnine; Swimming

Isolated brainstem preparations from larval (tadpole) and adult Rana catesbeiana were used to examine inhibitory mechanisms for developmental regulation of the respiratory central pattern generator (CPG). Preparations were superfused at 20-22 degrees C with Cl(-)-free artificial cerebrospinal fluid (aCSF) or with aCSF containing agonists/antagonists of gamma-aminobutyric acid (GABA) or glycine receptors. Respiratory motor output from the CPG, measured as neural activity from cranial nerve roots, was associated with fictive gill ventilation and lung ventilation in tadpoles and with fictive lung ventilation in adults. In tadpoles, fictive lung burst frequency was 0.8+/-0.2 min(-1) and did not change significantly with Cl(-)-free aCSF superfusion; however, lung burst amplitude increased by nearly 400 % (P<0.01). Fictive gill ventilation averaged 41.6+/-3.3 min(-1) and was reversibly abolished by Cl(-)-free aCSF. Superfusion with Cl(-)-free aCSF abolished lung bursts in two of seven adult preparations, and overall lung burst frequency decreased from 3.1+/-0.7 to 0.4+/-0.03 min(-1) (P<0.01), but burst amplitude was unchanged. Low concentrations of GABA (0.5 mmol l(-1)) produced a significant increase in lung burst frequency followed by almost complete inhibition at 5.0 mmol l(-1), accompanied by the abolition of gill ventilation at 2.5-5.0 mmol l(-1). By contrast, fictive lung ventilation in adults was inhibited in a dose-dependent manner by glycine and GABA, and inhibition occurred at approximately 10-fold lower concentrations compared with tadpoles. The glycine receptor antagonist strychnine (2.5-25.0 micromol l(-1)) and the GABA(A) receptor antagonist bicuculline (1-10 micromol l(-1)) inhibited fictive gill ventilation and increased fictive lung ventilation in tadpoles. However, bicuculline and strychnine inhibited fictive lung ventilation in adults. These results suggest that lung ventilation in the tadpole brainstem may be driven by a pacemaker-like mechanism since Cl(-)-free aCSF failed to abolish lung ventilation. Lung ventilation in adults and gill ventilation in tadpoles, however, appear to be dependent upon conventional Cl(-)-mediated synaptic inhibition. Thus, there may be a developmental change in the fundamental process driving lung ventilation in amphibians. We hypothesize that maturation of the bullfrog respiratory CPG reflects developmental changes in glycinergic and/or GABAergic synaptic inhibitory mechanisms.

Topics: Aging; Animals; Bicuculline; Body Weight; Brain Stem; Chlorides; In Vitro Techniques; Larva; Lung; Neurons; Rana catesbeiana; Receptors, Glycine; Respiratory Mechanics; Spinal Nerves; Strychnine

Separate, 28-day, subchronic studies of strychnine dietary toxicity were conducted using northern bobwhite quail (Colinus virginianus) and mallard ducks (Anas platyrhynchos). Five groups (five males five females/group) of 29-week-old quail were fed Purina(R) Game Bird Breeder Layena(R) diets containing mean (+/-SD) 484.2 (+/-17.0), 972. 6 (+/-54.0), 1,870.8 (+/-176.1), 3,516.7 (+/-68.0), and 6,083.3 (+/-269.6) microgram/g strychnine; whereas five groups of 27-week-old mallards (five males five females/group) were fed similar diets containing mean (+/-SD) 18.8 (+/-1.3), 91.1 (+/-27.3), 235.0 (+/-33. 8), 484.2 (+/-17.0), and 972.6 (+/-54.0) microgram/g strychnine. Separate "vehicle control" (0.0 microgram/g strychnine) groups (five males, five females/group) were included in each study. Strychnine toxicity was much less pronounced in quail; no observed effect concentrations (NOECs) were 972.6 (+/-54.0) and 91.1 (+/-27.3) microgram/g strychnine for quail and ducks, respectively. Several possible explanations for the species effects are offered, and some practical issues affecting the conduct of long-term, dietary toxicity studies are discussed.

Topics: Animals; Body Weight; Colinus; Diet; Ducks; Female; Male; Poisons; Strychnine

The gamma 2 subunit of the gamma-aminobutyric acid type-A (GABAA) receptor is associated with the actions of benzodiazepines and related drugs. A phosphorothioate-modified antisense oligodeoxynucleotide directed against the gamma 2 subunit was given by i.c.v. injection (18 micrograms in 2 microliters saline) to male Sprague-Dawley rats every 12 h for 3 days. Controls received the corresponding sense oligodeoxynucleotide. 4-6 h after the last i.c.v. treatment, rats were given methyl-beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine "inverse agonist', by slow i.v. infusion. Compared to naive rats, the beta-CCM threshold dose was not affected by the sense oligodeoxynucleotide, but was increased 87% in antisense oligodeoxynucleotide-treated rats. The treatment had no effect on the seizure threshold for picrotoxin. Both antisense and sense oligodeoxynucleotide treatments slightly increased the threshold for strychnine seizures. The results suggest that antisense oligodeoxynucleotide treatment altered GABAA receptor composition and interfered with the actions of a benzodiazepine receptor ligand in vivo, and may provide a tool for studying regulation of receptor structure and function.

Topics: Analysis of Variance; Animals; Body Weight; Carbolines; Convulsants; Injections, Intraventricular; Male; Oligonucleotides, Antisense; Picrotoxin; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; RNA, Messenger; Seizures; Strychnine

Glycine and glutamate binding sites are allosterically coupled at the N-methyl-D-aspartate (NMDA) receptor complex. Previous studies have shown that antagonism of glutamate at the NMDA receptor reduces the minimum alveolar concentration (MAC) for volatile anesthetics. 5-Nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA-1021) is a competitive antagonist at the glycine recognition site of the NMDA receptor. The purpose of this study was to determine whether glycine receptor antagonism also reduces volatile anesthetic requirements in the rat.. In experiment 1, Sprague-Dawley rats were anesthetized with halothane in 50% O2-balance N2 and their lungs mechanically ventilated. They were randomly assigned to one of three groups according to the dose of ACEA-1021 administered (0, 20, or 40 mg/kg intravenously; n = 6). The bolus dose of ACEA-1021 was followed by a continuous intravenous infusion of vehicle or ACEA-1021 at 14 mg.kg-1.h-1. Halothane MAC was then determined by the tail-clamp method. In experiment 2, awake rats were randomly assigned to groups according to the same dosages of ACEA-1021 as in experiment 1. Arterial CO2 tension and mean arterial pressure were recorded before and 5 and 30 min after the start of the infusion. The infusion was then stopped, and the time to recovery of the righting reflex was recorded.. In experiment 1, ACEA-1021 decreased halothane MAC (mean +/- SD) in a dose-dependent manner (control, 0.95 +/- 0.15 vol%; ACEA-1021 20 mg/kg, 0.50 +/- 0.14 vol%; ACEA-1021 40 mg/kg, 0.14 +/- 0.16 vol%; P < 0.01). In experiment 2, arterial CO2 tension was increased by ACEA-1021 (control, 38 +/- 3 mmHg; ACEA-1021 20 mg/kg, 43 +/- 3 mmHg; ACEA-1021 40 mg/kg, 48 +/- 2 mmHg; P < 0.01). Mean arterial pressure was not affected by any dose of ACEA-1021. The righting reflex was abolished in rats receiving ACEA-1021 40 mg/kg only and recovered 30 +/- 7 min after discontinuation of the infusion.. Halothane MAC reduction by glycine receptor antagonism was greater than that previously observed for antagonism of glutamate at the NMDA or AMPA receptor. In rats receiving ACEA-1021 only, minimal hemodynamic depression and moderate hypoventilation were observed. Antagonism of glycine at the NMDA receptor recognition site offers a potential mechanism of action of anesthesia.

Topics: Animals; Binding, Competitive; Blood Pressure; Body Weight; Carbon Dioxide; Drug Interactions; Glycine; Halothane; Hydrogen-Ion Concentration; Male; Oxygen; Partial Pressure; Pulmonary Alveoli; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Glycine; Receptors, N-Methyl-D-Aspartate; Strychnine

Topics: Aging; Animals; Animals, Newborn; Avoidance Learning; Body Weight; Electroshock; Female; Handling, Psychological; Male; Rats; Sex Factors; Strychnine

Topics: Animals; Body Weight; Enzyme Induction; Hexobarbital; Male; Microsomes, Liver; Organ Size; Phenobarbital; Portacaval Shunt, Surgical; Rats; Rats, Inbred Strains; Strychnine; Time Factors

Topics: Aging; Aminopyrine; Anesthesia; Aniline Compounds; Animals; Body Weight; Cytochromes; Electron Transport; Hexobarbital; In Vitro Techniques; Mice; Microsomes, Liver; Nitrobenzenes; Oxidoreductases; Paralysis; Strychnine; Zoxazolamine

Topics: Allopurinol; Aminocaproates; Analgesics; Animals; Antineoplastic Agents; Azathioprine; Body Weight; Chloroquine; Colchicine; Cortisone; Cyclophosphamide; Cyproheptadine; Diazoxide; Dimethyl Sulfoxide; Encephalomyelitis, Autoimmune, Experimental; Hydrocortisone; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Methyldopa; Nialamide; Oils; Organ Size; Rats; Strychnine; Talc; Thalidomide; Thioguanine; Thiomalates

Topics: Aminopyrine; Aniline Compounds; Animals; Body Weight; Caseins; Dietary Proteins; Electron Transport; Female; Liver; Male; Microsomes; NADP; Organ Size; Pentobarbital; Rats; Sex Factors; Strychnine; Zoxazolamine

Topics: Aging; Aminobenzoates; Aminopyrine; Aniline Compounds; Animals; Azo Compounds; Benzoates; Body Weight; Cytochromes; Electron Transport; Female; Hexobarbital; Liver; Male; Microsomes; NADP; Organ Size; Oxidation-Reduction; Oxidoreductases; Proteins; Rats; Sex Factors; Strychnine

Topics: Animals; Atropine; Body Weight; Female; Hexamethonium Compounds; Histamine; Injections; Male; Mice; Picrotoxin; Strychnine; Tetrodotoxin; Toxicology; Toxins, Biological; Tubocurarine

Topics: Amides; Anesthesia; Animals; Barbiturates; Body Weight; Carisoprodol; Diphosphates; Female; Hexobarbital; Kidney; Liver; Male; Organ Size; Paralysis; Pentobarbital; Phenobarbital; Rats; Starvation; Strychnine; Sucrose; Zoxazolamine