ABSTRACT
OBJECTIVE@#To investigate the effects of aminooxyacetic acid (AOAA) on learning and memory ability and possible mechanisms in rats with chronic alcoholism.@*METHODS@#Sixty SD male rats were randomly divided into three groups on average.The model group rats and the remedy group rats were fed with the water containing (v/v) 6% alcohol for 28 days.After 14 days, the remedy group rats were treated with AOAA (5 mg/kg·d) by intraperitoneal injection once a day for 14 days and the other two group rats were treated with the equal amount of saline by intraperitoneal injection every day.Five days before the end of the experiment, the water maze test was carried out to test the learning and memory ability of rats for 5 days.Subsequently, the content of HS, the activity of ATP enzyme and the expression of 5-HT in hippocampus were measured.@*RESULTS@#Compared with the rats in the control group, the latency and the swimming distance of the 2nd to the 4th day, the content of HS in hippocampus of rats in the model group were all increased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were decreased (<0.01).Compared with the rats in the model group, the latency and the swimming distance of the 2nd to the 4th day, the content of HS in hippocampus of the rats in the remedy group were decreased, the mitochondrial ATP enzyme activity in hippocampus and the positive expression of 5-HT in hippocampus CA1 and CA3 of rats in the model group were increased (<0.01).@*CONCLUSIONS@#AOAA could alleviate the symptoms of chronic alcoholism rats, which may be related to the effects of AOAA on the content of HS, the mitochondrial enzyme activity and the expression of 5-HT in hippocampus.
Subject(s)
Animals , Male , Rats , Alcoholism , Aminooxyacetic Acid , Hippocampus , Learning , Maze Learning , Memory , Rats, Sprague-DawleyABSTRACT
BACKGROUND/AIMS: The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. METHODS: Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. RESULTS: Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 muM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 muM). Contractile responses were also reduced (by 45% at 5 Hz, P carbon monoxide > hydrogen sulfide.
Subject(s)
Adenosine Triphosphate , Adrenergic Neurons , Aminooxyacetic Acid , Anal Canal , Atropine , Autonomic Pathways , Carbon Monoxide , Carbon , Gases , Guanethidine , Hydrogen Sulfide , Hydrogen , Indomethacin , Neurotransmitter Agents , Nitric Oxide , Norepinephrine , Prostaglandin-Endoperoxide Synthases , Purinergic Antagonists , Receptors, Muscarinic , Receptors, Purinergic , Relaxation , Suramin , Vasoactive Intestinal Peptide , ZincABSTRACT
A monoclonal antibody (mAb) against zearalenone (ZEN) was produced using ZEN-carboxymethoxylamine and -BSA conjugates. Antibody produced by one clone showing a very high binding ability was selected and found to have a higher affinity for ZEN compared to a commerciall ZEN antibody. We developed two direct competitive ELISA systems using the selected antibody (ZEN-coated and anti-ZEN antibody-coated ELISA). Quantitative ranges for the anti-ZEN antibody-coated ELISA and ZEN-coated ELISA were from 25 to 750 ppb and from 12.5 to 100 ppb, respectively. The detection limit of both methods as measured with standard solutions was 10 ppb. The intra-plate and inter-well variation of both ELISAs were less than 10%. The IC50 values for alpha-zearalenol, beta-zearalenol, alpha-zearalanol, and beta-zearalanol compared to ZEN were 108.1, 119.3, 114.1, and 130.3% for the ZEN-coated ELISA. These values were 100.7, 120.7, 121.6, and 151.6% for the anti-ZEN antibody-coated ELISA. According to the anti-ZEN antibody-coated ELISA, the average recovery rates of ZEN from spiked animal feed containing 150 to 600 ng/mL of ZEN ranged from 106.07 to 123.00% with 0.93 to 2.28% coefficients of variation. Our results demonstrate that the mAb developed in this study could be used to simultaneously screen for ZEN and its metabolites in feed.
Subject(s)
Animals , Female , Mice , Aminooxyacetic Acid/chemistry , Antibodies, Monoclonal/immunology , Enzyme-Linked Immunosorbent Assay/methods , Inhibitory Concentration 50 , Mice, Inbred BALB C , Reproducibility of Results , Serum Albumin, Bovine/chemistry , Zearalenone/immunologyABSTRACT
Evaluamos 1) efecto del tratamiento prolongado (días 23-29 postnatales) con ácido aminooxiacético (AAOA) sobre el desarrollo puberal en ratas hembra; este tratamiento aumentó el contenido de GABA (p< 0.002), disminuyendo el de GnRH y glutamato (p < 0.05 y < 0.02) en hipotálamo. La LH (p < 0.05) y el estradiol (p < 0.005) séricos cayeron. La apertura vaginal fue a los 30.8 + 0.6 días en los controles, y a los 36.7 + 0.98 días en las tratadas (p < 0.0001). 2) A los 30 días, el tratamiento agudo con AAOA redujo la liberación ex vivo de GnRH y de glutamato la de taurina. Este efecto fue similar al observado agregando al medio agonistas GABA-A y B. Conclusiones: la activación peripuberal del sistema GABAérgico frena el eje reprodutor, produciendo un retraso en el desarrollo. Esto podría atribuirse a la existencia, en esta etapa, de interrelaciones fisiológicas entre los aminoácidos que regulan la secreción de GnRH (GABA, glutamato, taurina).
Subject(s)
Animals , Female , Rats , /physiology , Aminooxyacetic Acid/administration & dosage , Animals, Newborn , GABA Agents/administration & dosage , gamma-Aminobutyric Acid/drug effects , Case-Control Studies , Estradiol/blood , gamma-Aminobutyric Acid/metabolism , Gonadotropin-Releasing Hormone/metabolism , Rats, Wistar , Taurine/metabolismABSTRACT
Pretreatment with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT, antagonised while pretreatment with p-chlorophenylalanine (PCPA), a 5-HT depletor, potentiated the myoclonus induced by picrotoxin, a GABA antagonist. Pretreatment with aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, antagonised picrotoxin-induced myoclonus. The combined effect of the least protective doses of AOAA and 5-HTP was greater than the sum of their individual inhibitory effects on picrotoxin-induced myoclonus. Further, AOAA failed to inhibit picrotoxin-induced myoclonus in PCPA pretreated rats. These findings suggest that the central 5-HT-ergic system exerts a facilitatory influence on the GABA-ergic system and thus it is involved in the antimyoclonic action of GABA.
Subject(s)
5-Hydroxytryptophan/pharmacology , Aminooxyacetic Acid/pharmacology , Animals , Fenclonine/pharmacology , Male , Myoclonus/chemically induced , Picrotoxin/antagonists & inhibitors , Rats , Rats, Inbred Strains , Serotonin/pharmacology , gamma-Aminobutyric Acid/pharmacologyABSTRACT
The effect of propranolol was assessed against myoclonus induced by picrotoxin (a known GABA antagonist) in a dose of 3 mg/kg and allylglycine (the inhibitor of GABA synthesis and release) in a dose of 150 mg/kg. A dose-dependent (0.5-2 mg/kg) protective effect was found against both models. Pretreatment of rats with a GABA-reducing dose (100 mg/kg, nonmyoclonic) of allylglycine produced no change in the effect of propranolol against picrotoxin-induced myoclonus. Propranolol thus inhibited myoclonic responses when both the receptor activity and the functional pool of GABA were impaired, suggesting that it produces as antimyoclonic action without the involvement of GABA. However, the drug seems to show a synergistic action with GABA-ergic agents, as greater protection was observed in rats treated concurrently with propranolol and amino-oxyacetic acid, an inhibitor of GABA degradation.
Subject(s)
Acetates/therapeutic use , Aminooxyacetic Acid/therapeutic use , Animals , Drug Synergism , Male , Myoclonus/chemically induced , Picrotoxin/toxicity , Propranolol/therapeutic use , Rats , Rats, Inbred StrainsABSTRACT
The present study investigates whether clonazepam exerts its antimyoclonic action through a GABA independent mechanism. We have studied the antimyoclonic effect of clonazepam and compared it with that of aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, against myoclonus induced by picrotoxin, a GABA receptor antagonist and allylglycine, a drug which inhibits synthesis and release of GABA. We have also investigated the effect of clonazepam against picrotoxin-induced myoclonus in rats pretreated with either AOAA or submyoclonic dose of allylgylycine. Clonazepam pretreatment inhibited both picrotoxin and allylglycine-induced myoelonus whereas AOAA was effective in inhibiting only picrotoxin-induced myoclonus. The protective effect of clonazepam against picrotoxin-induced myoclonus was potentiated by AOAA pretreatment. Moreover, clonazepam afforded protection against picrotoxin-induced myoclonus in rats pretreated with a submyoclonic GABA reducing dose of allylglycine. These findings indicate that a GABA independent mechanism may also be involved in the antimyoclonic action of clonazepam.
Subject(s)
4-Aminobutyrate Transaminase/metabolism , Allylglycine , Aminooxyacetic Acid , Animals , Anticonvulsants , Brain Chemistry/drug effects , Clonazepam/pharmacology , Male , Myoclonus/chemically induced , Picrotoxin , Rats , Rats, Inbred Strains , gamma-Aminobutyric Acid/metabolismABSTRACT
A delay in the onset of isoniazid-induced convulsions was found in rats pretreated with the beta 2-adrenoceptor blocker, butoxamine and the nonspecific beta-blocker, propranolol. In these animals the convulsive responses were inhibited in a dose dependent manner. These compounds were found to be effective even after the induction of convulsions. The beta 1-blocker, acebutolol was able to protect rats only when injected prior to the challenge. The anticonvulsant effect of acebutolol and propranolol but not that of butoxamine was found to be enhanced in animals pretreated with a gamma-aminobutyric acid (GABA) elevating agent, aminooxyacetic acid (AOAA). The findings indicate that the GABA-mediated anticonvulsant action of AOAA seems to be additive with that resulting from beta 1 but not beta 2-blockade.
Subject(s)
Acebutolol/pharmacology , Acetates/pharmacology , Adrenergic beta-Antagonists/pharmacology , Aminooxyacetic Acid/pharmacology , Animals , Anticonvulsants , Butoxamine/pharmacology , Isoniazid , Male , Propranolol/pharmacology , Rats , Rats, Inbred Strains , Seizures/chemically induced , gamma-Aminobutyric Acid/physiologyABSTRACT
The protective effect of two benzodiazepine compounds, diazepam and clonazepam was tested against isoniazid (INH)- induced convulsions in rats pretreated with the gamma-amino-butyric acid (GABA) transaminase inhibitor viz., aminooxyacetic acid (AOAA), and the result was compared with that produced by the two drugs independently. Rats treated 6 h and not 30 min previously with AOAA showed a dose-dependent inhibition of INH-induced convulsions. In these animals both diazepam and clonazepam showed a greater protective effect than that produced by them alone. It is suggested from these findings that, even if their anticonvulsant mechanisms are distinct, with or without the involvement of GABA, AOAA and the benzodiazepine compounds seem to act synergistically against INH-induced convulsions.
Subject(s)
Acetates/therapeutic use , Aminooxyacetic Acid/therapeutic use , Animals , Clonazepam/therapeutic use , Diazepam/therapeutic use , Drug Therapy, Combination , Isoniazid , Male , Rats , Rats, Inbred Strains , Seizures/chemically inducedABSTRACT
Hígados aislados de ratas alimentadas, fueron perfundidos con un medio preparado a partir de solución KRB a la cual se añadieron: seroalbúmina bovina, 3g/dl; glucosa, 90 mg/dl; ortofosfato para obtener una concentración en el plasma de 1 mg/dl; 18 por ciento de glóbulos rojos de rata lavados; pH, 7.40, fase gaseosa O2 95%-CO2 5%. Flujo 36 ml/min. Temperatura, 37-C. Volumen del perfusado 70 ml. 0,5 micronCi de 32P-ortofosfato por ml. fueron añadidos al perfusado diez minutos antes de montar el hígado: el tiempo, 15 minutos después de montar el órgano, se tomó como punto cero. En los experimentos en los cuales se emplearon los bloqueadores de la neoglucogénesis ( quinolinato 1,68 mM o aminoóxi-acetato 0.2 mM) éstos fueron añadidos al perfusado al tiempo 15 min. el glucagon, cuando fue administrado, se empleó en inyección continua entre 45 y 90 min. (20 microngm). Se tomaron muestras cada 15 minutos hasta 120 minutos, que se recogieron en tubos enfriados en hielo. Glucosa en el perfusado, Pi en el plasma, 32Pi en perfusado y actividad específica del Pi plasmático fueron los parámetros determinados. Se calcularon Deltas a partir de 45 min. Los valores de glucosa y de Pi plasmático se corrigieron a partir de blancos obtenidos, haciendo circular el perfusado en ausencia del hígado y los resultados se expresaron por 10g de hígado fresco