Metabolic Studies on the Mechanisms of Increased Susceptibility of Weanling Rats to Parathion

1972 ◽  
Vol 50 (9) ◽  
pp. 902-915 ◽  
Author(s):  
Jacques Gagné ◽  
Jules Brodeur
Keyword(s):  
Toxic Effects ◽  
Intravenous Route ◽  
Toxic Metabolite ◽  
Adult Males ◽  
Adult Rats ◽  
Renal Handling ◽  
Weanling Rats ◽  
The Brain ◽  
Increased Susceptibility

Equitoxic doses of 32P-parathion (1.5 mg/kg in weanlings of both sexes, 2.0 mg/kg in adult females, and 3.1 mg/kg in adult males) were given by the intravenous route to immature and adult rats in order to investigate the respective contribution of biotransformation, distribution, and excretion phenomena to the increased susceptibility of weanling rats to the acute toxic effects of parathion. At various intervals, the animals were sacrified and the amounts of parathion, paraoxon, diethylphosphorothioic acid, and diethylphosphoric acid in the liver, kidneys, tibial muscle, plasma, brain, adipose tissue, and urine were determined. In vitro metabolism of 32P-parathion by liver homogenates was also investigated. The results obtained suggest that weanlings are more susceptible to parathion than adults mainly because of deficient hepatic mechanisms for degradation of parathion and its toxic metabolite, paraoxon. In addition, the brain tissue of weanlings appears to be more sensitive to the toxic effects of paraoxon than the brain of male adults. On the other hand, the passage of parathion and paraoxon across the blood–brain barrier does not seem to be facilitated in weanlings by comparison with adults. Finally, there is no evidence that the renal handling of parathion and its metabolites might influence the acute toxicity of parathion in weanling and adult rats.

Development in rats of the brain-pituitary-adrenal response to hypoglycemia in vivo and in vitro

1989 ◽  
Vol 257 (5) ◽  
pp. E757-E763 ◽  
Author(s):  
E. P. Widmaier
Keyword(s):  
Base Line ◽  
Adult Rats ◽  
Glucose Levels ◽  
Altered Glucose ◽  
Dose Dependent Fashion ◽  
Adrenal Response ◽  
Old Rats ◽  
The Brain

To clarify the nature of the stress hyporesponsive period that occurs in neonatal rats, the development of the response of the brain-pituitary-adrenal axis to hypoglycemia stress in rats was assessed in vivo and in vitro. Hypothalami were removed from the brains of neonatal (9-35 days postnatal) or adult rats and incubated in vitro for sequential 30-min periods in Krebs buffer for determination of corticotropin-releasing factor (CRF) secretion under conditions of altered glucose concentrations. As expected from previous studies, CRF secretion from adult hypothalami was significantly increased in severely hypoglycemic conditions (0.55 mM glucose) by approximately 50% above base-line values (in 5.5 mM glucose). However, lowering glucose did not elicit an increase in CRF release from hypothalami of rats less than 35 days of age. Hypothalami obtained from rats less than or equal to 24 days old also failed to show consistent secretory responses to potassium depolarization. At 35 days postnatal the response to hypoglycemia was significant and similar to the adult response. To determine if the lack of hypothalamic response to hypoglycemia in vitro could be correlated with the in vivo responses to hypoglycemia, rats aged 4 days to adult were injected intraperitoneally with porcine insulin and killed at different times after injection. Insulin injections lowered plasma glucose levels in fasted 4-day-old rats in a dose-dependent fashion, but a nadir in glucose (approximately 40 mg/dl) was not reached until 90 min; the same treatment produced a nadir in glucose within 30 min in fasted rats 10 days old and older, suggesting that the 4-day-old rats are relatively insulin insensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Leptin inhibits testosterone secretion from adult rat testis in vitro

1999 ◽  
Vol 161 (2) ◽  
pp. 211-218 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
C Dieguez ◽  
FF Casanueva ◽  
...  
Keyword(s):  
Adult Male ◽  
Reproductive Function ◽  
Serum Testosterone ◽  
Testicular Tissue ◽  
Male Rats ◽  
Adult Males ◽  
Adult Rats ◽  
Adult Rat ◽  
Testosterone Secretion

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed adult rats. In addition, 10(-9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries from fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the state of sexual maturation, is able to inhibit testosterone secretion acting at the testicular level. Furthermore, the present data suggest that the actions of leptin on the reproductive system are complex and are probably carried out at different levels of the hypothalamic-pituitary-gonadal axis.

Ontogenesis of intestinal bile salt absorption in the neonatal rat

1980 ◽  
Vol 239 (4) ◽  
pp. G319-G323 ◽  
Author(s):  
J. M. Little ◽  
R. Lester
Keyword(s):  
Bile Salt ◽  
Steroid Treatment ◽  
Neonatal Rat ◽  
Metabolic Inhibitors ◽  
Ileal Mucosa ◽  
Adult Rats ◽  
Salt Absorption ◽  
Weanling Rats ◽  
Mucosal Uptake

In vitro uptake of taurocholate by weanling rat ileum was characterized. The neonatal development of the ileal mechanism was determined, and the effect of steroid treatment on this development was assessed. Mucosal uptake of taurocholate by ileum of 26-day-old and adult rats was linear with time and, when measured as a function of concentration, tended toward a plateau. Mucosal concentration of taurocholate was significantly reduced by metabolic inhibitors and was competitively inhibited by taurochenodeoxycholate. The capacity to concentrate taurocholate in ileal mucosa was undemonstrable in 12-day-old neonates, first appeared at 15 days, and reached adult levels by 26 days of age. Mucosal uptake of taurocholate by ileum of 12-day-old offspring of steroid-treated mothers or of 12-day-old neonates given dexamethasone directly was significantly increased over control values. The results indicate that the ileal bile salt absorption found in weanling rats is an active process that does not begin to develop in neonatal rats until 15 days after birth, and that the appearance of ileal active transport can be accelerated by maternal or neonatal steroid treatment.

THE EFFECTS OF X-IRRADIATION ON PROTEIN METABOLISM OF THE BRAIN

1965 ◽  
Vol 43 (7) ◽  
pp. 1091-1098 ◽  
Author(s):  
Shozo Nakazawa ◽  
Takao Hara ◽  
Komei Ueki
Keyword(s):  
Rat Brain ◽  
Protein Metabolism ◽  
Leucine Incorporation ◽  
Adult Rats ◽  
Rat Brain And Liver ◽  
Glucose Incorporation ◽  
X Irradiation ◽  
Total Body ◽  
The Brain

The effects of X-irradiation on the metabolism of rat brain, liver, and spleen have been studied. C14-Glucose incorporation into protein of the brain of newborn rats was affected significantly by total body X-irradiation (250 r each day for 4 days). C14-Leucine incorporation into protein of the brain, liver, and spleen of adult rats was also reduced by total body X-irradiation (300 r each day for 4 days).X-irradiation of the head (500 r each day for 6 days) affected C14-leucine incorporation into protein of rat brain and liver, but it did not affect that of spleen.X-irradiation in vitro (5000 r) did not have any effect on protein metabolism of rat brain. The mode of action of X-irradiation on protein metabolism is discussed.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

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