Differential responses of regional brain polyamines following in utero exposure to synthetic pyrethroid insecticides: a preliminary report.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
P K Seth
Publications and source records attributed to P K Seth.
Protein malnourishment: a predisposing factor in acrylamide toxicity in pregnant rats.
Exposure to acrylamide (3-10 mg/kg body weight) was found to be lethal for protein-deficient pregnant rats as evidenced by their increased mortality. It had no such effect on the normal protein diet fed pregnant and nonpregnant rats and the protein-malnourished nonpregnant rats. Protein deficiency during pregnancy caused a significant decrease in the activity of brain monoamine oxidase and acetylcholinesterase and striatal [3H]spiperone binding, known to label dopamine receptors; had no significant effect on the binding of 3H-QNB (quinuclidinyl benzilate) to cerebellar and [3H]diazepam to frontocortical membranes, known to label muscarinic and benzodiazepine receptors, respectively; and had no significant effect on brain glutathione (GSH) levels in comparison with pregnant rats fed normal protein diet. Exposure to acrylamide (2 mg/kg body weight) in protein-malnourished pregnant rats caused a marked decrease in the activity of monoamine oxidase and acetylcholinesterase and also in the binding of [3H]spiperone, [3H]QNB, and [3H]diazepam to striatal, cerebellar, and frontocortical membranes, respectively. Kinetic studies revealed that decreased binding of these ligands in the specific brain regions were due to decreased receptor sites (Bmax). A reduction in the brain glutathione content was also observed in these animals in comparison with those fed a low-protein diet during pregnancy. Pregnant rats fed a normal-protein diet on acrylamide exposure, however, showed no such biochemical changes in comparison with the pregnant rats fed normal protein diet. Also, no effect on any of the parameters studied was observed in the adult nonpregnant rats fed a low-protein diet (for 18 d) and those exposed to the monomer (d 6-17) fed either a normal- or low-protein diet in comparison with respective controls. The results indicate that pregnancy under conditions of malnutrition modifies the susceptibility of pregnant rats toward acrylamide.
Acetylcholinesterase↗
Biochemical and morphological studies in testes of rat offspring of mothers exposed to styrene during lactation.
Explore the source record for details and available documents.
Animals↗
Altered activity of hepatic mixed function oxidase, cytochrome P-450 and glutathione-S-transferase by styrene in rat fetal liver.
The effect of in utero exposure to styrene 200 or 400 mg/kg/day orally was studied on mixed function oxidase activities, cytochrome P-450 and glutathione contents and on the glutathione-S-transferase activity in rat fetal liver. Activities of aminopyrene-N-demethylase, aniline hydroxylase, aryl hydrocarbon hydroxylase and the cytochrome P-450 contents were significantly decreased in the fetal liver. A significant decrease in the glutathione contents and the glutathione-S-transferase activity was also observed in the liver of the fetuses of styrene exposed animals. The current data show that prenatal exposure to styrene could adversely affect the developing biotransformation process.
Animals↗
The influence of low protein diet on the testicular toxicity of di(2-ethylhexyl)phthalate.
Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight to adult male albino rats maintained on low protein (LP) diet for 15 d resulted in a greater decrease in absolute and relative weights of the testis and in epididymal sperm count than in those rats maintained on a normal protein (NP) diet. A marked increase in the activity of testicular beta-glucuronidase and gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed animals on exposure to DEHP suggested that LP diets enhance the susceptibility of the testis towards DEHP.
Administration, Oral↗
Effect of styrene on testicular enzymes of growing rat.
Effect of styrene (100 or 200 mg/kg body wt/day) for 60 days was observed on testicular enzymes of postnatally maturing rats. A significant decrease in epididymal spermatozoa count was observed only at 200 mg/kg body weight dose. Activities of testicular sorbitol dehydrogenase and acid phosphatase decreased while activities of lactate dehydrogenase, beta-glucuronidase, glucose-6-phosphate dehydrogenase, and gamma-glutamyl transpeptidase significantly increased only in animals exposed to styrene at a dose of 200 mg/kg body weight. The results suggest that exposure to high dose of styrene during developmental period alters the activities of enzymes associated with specific cell type of testis.
Animals↗
Prevalence of malaria in Ao Nagas and its association with G6PD and HbE.
Glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin E (HbE) were studied among 708 malarial patients and control groups of Ao Nagas from the Mokokchung District of Nagaland in the extreme northeast of India. The data suggest that malaria is an important ecologic factor in maintaining the high frequency of G6PD deficiency and HbE among the Ao Nagas. Although migrations from adjoining populations that have a high frequency of both these traits could have contributed to the presence of these genes in the Ao Nagas, malaria also could be an essential determinant in maintaining the current high frequency in present-day Ao Nagas.
Ethnicity↗
Central muscarinic receptor subtypes and carrageenin-induced paw oedema in rats.
In an earlier report from this laboratory, it was demonstrated that the central cholinergic system exerted a modulatory pro-inflammatory effect on carrageenin-induced paw inflammation in rats. In this study, the role of the central muscarinic receptors in cholinergic modulation of peripheral inflammation was investigated by using several M1 and M2 receptor agonists and antagonists. The M1 receptor agonists aceclidine and arecholine and the nonspecific muscarinic receptor agonist oxotremorine augmented carrageenin oedema, an effect attenuated by the M1 receptor antagonist scopolamine. Physostigmine behaved like a M1 receptor agonist at all dose levels. However, the other M2 receptor agonist, carbachol, produced a dose-dependent dual effect, with lower doses attenuating the oedema and higher doses augmenting the inflammation. While the former action appeared to be due to M2 receptor stimulation, because it was blocked by AF-DX 116--a M2 receptor antagonist, the latter action appeared to be induced by M1 receptor stimulation, because it was inhibited by scopolamine. The pro-inflammatory effect of the M2 receptor antagonists AF-DX 116 and gallamine appeared to be induced by enhanced neuronal release of acetylcholine, because the effects were not evident following pretreatment with hemicholinium, which attenuates synthesis of the amine. Muscarinic receptor binding studies with (3H)-QNB indicated that the corpus striatum has substantially higher population of M1 receptors compared with the cerebellum. In the corpus striatum, (3H)-QNB binding indicated initial up-regulation followed by down-regulation of M1 receptors during peak inflammation, which appeared to persist even after a decrease in the inflammation. In contrast, the M1 receptors in the cerebellum appeared to be down-regulated very transiently during the early phase of the inflammation. While these receptor alterations may be due to the inflammation, it is equally possible that they represent changes induced by the stress of pain and inflammation induced by carrageenin.
Animals↗
Human choriogonadotropin-induced coupling of receptor and Gs protein and the effect of hormone deglycosylation.
The detergent-soluble extract of rat ovary plasma membranes contained a Gs protein of about 100 kDa as shown by its elution behavior on a Bio Gel A-1.5m column. However, the cell membranes exposed to hCG (37 degrees C, 15 min) contained in addition a higher molecular weight Gs protein complex of 300 kDa comprised of human chorionic gonadotropin (hCG) receptor (hCGR) and Gs. The complex bound with an affinity column of GTP-Sepharose and could be released with Gpp(NH)p and GTP inhibited this binding. The presence of the hCGR in the complex was shown by its binding to 125I-hCG. Furthermore, GTP inhibited the binding of hCG to the complex. These results indicate the presence of hCGR and Gs protein complex in the hCG-treated membranes. hCGR and Gs protein were individually purified and reconstituted into phospholipid vesicles. The protein-phospholipid vesicles showed saturation kinetics of binding of 125I-hCG and 3H-Gpp(NH)p. Incubation of phospholipid vesicles with hCG resulted in a 2-3-fold increase in the binding of 3H-Gpp(NH)p and GTPase activity. Activation of Gs protein was dependent on the length of incubation and the hormone concentration. Deglycosylated hCG was about 10 times less potent than hCG suggesting a role of carbohydrates of hCG in inducing hCG-Gs protein interactions. The data with the in vitro reconstitution system rule out the involvement of a carbohydrate-binding lectin in the function of the hormone.
Animals↗
Effect of dibutyltin dilaurate on regional brain polyamines in rats.
Administration of dibutyltin dilaurate (DBTL; 0, 20 or 40 mg/kg body wt.) by gavage to rats for 3 consecutive days produced a significant increase in polyamine levels in selected brain areas. At the higher dose of DBTL (40 mg/kg) spermidine levels were raised in pons-medulla, hypothalamus and frontal cortex while spermine levels increased in pons-medulla, hippocampus and frontal cortex regions. At the lower dose (20 mg/kg) only a slight increase in polyamine levels occurred. The observed induction in regional brain polyamines in DBTL-treated rats may lead to disturbances in synaptic function and further enhance its neurotoxic potential.
Animals↗
Reduction of phosphoinositides and diacylglycerol levels in repeatedly dibutyltin-dilaurate-treated rat brain.
Oral administration of a single dose of dibutyltin dilaurate (DBTL, 80 mg/kg body wt.), 2 or 24 h after treatment, caused no significant change in the levels of diacylglycerol and phosphoinositides in rat cerebrum (forebrain), whereas daily administration of DBTL (40 or 80 mg/kg body wt.) for 3 days (24 h after the final treatment) decreased the levels of diacylglycerol and phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate) in a concentration-dependent manner without influencing the levels of phosphatidylcholine in rat cerebrum. These studies indicate impairment of the phosphoinositide messenger system in rat cerebrum following repeated exposure to DBTL.
Animals↗
Duffy blood groups and malaria in the Ao Nagas in Nagaland, India.
Blood samples from 324 malarial patients and 384 healthy individuals belonging to the Ao tribal community have been examined for Duffy blood group systems. The complete absence of Duffy-negative individuals among the Ao Nagas suggests that selection for resistance to vivax malaria by means of the Duffy-negative phenotype has not been available in the southeast Asian regions including the Ao Nagas.
Duffy Blood-Group System↗
Platelet aggregation in patients with Parkinson's disease.
Explore the source record for details and available documents.
Humans↗
Influence of mancozeb on mitogenically responsive lipids in rat cerebrum and liver.
Mancozeb, a commonly used fungicide, has been shown to induce tumours in mouse skin and maneb, unit constituent of mancozeb, is reported to induce tumours in rats. The mechanism by which mancozeb induced tumorigenicity is not known. Since the levels of inositol phospholipids and phosphatidic acid have roles in the regulation of cell proliferation, the effects of mancozeb on the levels of these lipids were studied in rats. Daily oral administration of commercial grade mancozeb at a concentration of 50 mg/kg body wt for 30 days (5 days a week) caused no significant change in the levels of inositol phospholipids and phosphatidic acid (PA) in both cerebrum and liver, while at high concentration (250 mg/kg body wt) under the same treatment schedule mancozeb increased the levels of these lipids. In cerebrum, the levels of phosphatidylinositol (PI) and PA were increased by 36 and 43% respectively without affecting the levels of polyphosphoinositides, whereas in liver the levels of not only PI (50%) and PA (49%) but also those of polyphosphoinositides were increased. These results show that mancozeb influences the levels of PA and inositol phospholipids, involved in phospholipase C-pathway of signalling.
Animals↗
Effect of in utero exposure to di(2-ethylhexyl)phthalate on rat testes.
In utero exposure to di(2-ethylhexyl)phthalate (DEHP; 1000 mg/kg body weight) significantly decreased activities of testicular sorbitol dehydrogenase and acid phosphatase and increased gamma-glutamyl transpeptidase, lactate dehydrogenase and beta-glucuronidase activities at early ages. A decrease in the sperm count of the epididymal spermatozoa was also observed in the sexually matured animals of DEHP exposed group. The data suggest that in utero exposure to DEHP may affect the normal development of testes.
Animals↗
Neurotoxicological effects of a pyrethroid formulation, fenvalerate in rats.
The effect of systemic treatment of a synthetic pyrethroid insecticide, fenvalerate (FV) was examined in adult female rats at different doses i.e. 5, 10, 20 mg/kg body weight by gavage for 21 consecutive days on regional brain levels of noradrenaline (NA), dopamine (DA), their acid metabolites: dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by HPLC-EC system. Our results demonstrate pronounced inhibition of NA, DA, HVA & DOPAC levels in several brain regions which were neither dose related nor region specific.
Animals↗
Cytochrome P-450 dependent monooxygenases in neuronal and glial cells: inducibility and specificity.
Distribution of the mixed function oxidases (MFO's) catalyzed by presence of multiple forms of cytochrome P-450 (P-450) was investigated in the neuronal and glial cells of the brain. The neuronal cells exhibited 2-3 fold higher activity of P-450 dependent arylhydrocarbon hydroxylase (AHH), 7-ethoxycoumarin-o-deethylase (ECOD) and 7-ethoxy-resorufn-o-deethylase (EROD) than the glial cells. Pretreatment with phenobarbital (PB) significantly increased (60-85%) the activity of ECOD in neuronal and glial cells, while a 140% increase was observed in neuronal AHH activity. Exposure to 3-methylcholanthrene (MC) resulted in a significant induction of the activity of AHH (102-345%), ECOD (115-150%) and EROD (75-120%) in the neuronal and glial cell preparations. The neurons, in general, exhibited greater sensitivity towards PB and MC induction. The present data indicate the differential sensitivity of these enzymes in neuronal and glial cells which could be used as a model to understand the selective action of certain neurotoxic agents.
7-Alkoxycoumarin O-Dealkylase↗
Influence of stress on phosphoinositides in rat brain.
The effect of a single 1 h immobilization or repeated 1 h immobilization for 10 days on the levels of phosphoinositides in rat whole brain was investigated. Immediately after 1 h immobilization the levels of phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) were decreased by 22 and 31%, respectively, but phosphatidylinositol 4-phosphate (PIP) was not significantly reduced. These changes were restored to normal levels 20 h after the immobilization. After repeated daily immobilizations the effect of stress on phosphoinositides was no longer observed. These results show that acute stress perturbs the concentration of PIP2 (precursor of second messengers) and indicate adaptation to acute stress in animals subjected to repeated stress.
Animals↗