p-Chlorophenyl Methyl Sulfide, p-Chlorophenyl Methyl Sulfoxide, and p-Chlorophenyl Methyl Sulfone. III. Toxicokinetics and Metabolism in Rats and Rhesus Monkeys

1993 ◽  
Vol 12 (4) ◽  
pp. 397-407 ◽  
Author(s):  
Jack C. Dacre ◽  
A. Philip Leber ◽  
Dennis C. Mays
Keyword(s):  
Rhesus Monkeys ◽  
Day Treatment ◽  
Sleep Time ◽  
Water Soluble ◽  
Blood Levels ◽  
Dependent Manner ◽  
Metabolite Formation ◽  
Methyl Sulfide ◽  
Methyl Sulfoxide ◽  
Test Materials

Pharmacokinetic properties of p-chlorophenyl methyl sulfide, p-chlorophenyl methyl sulfoxide, and p-chlorophenyl methyl sulfone were evaluated in rats and rhesus monkeys following oral administration of 14C radiolabeled test materials. In addition, urinary metabolite formation in treated rats was partially assessed, as was microsomal enzyme induction as determined by hexobarbital sleep time assays. All test materials were found to be rapidly absorbed following gavage dosing with a biphasic diminution of blood radiolabel in the rat. As an apparent result of higher dosage levels, rhesus monkeys exhibited both a delayed attainment of peak blood levels and a lower rate of elimination of blood 14C. A minor portion (5–7%) of urinary radioactivity from treated rats was not extractable with chloroform until incubation with deconjugation enzymes was conducted, releasing up to 50%. The values for rhesus monkeys were 15–62% and 50%, respectively; the former values are apparently elevated (relative to rat) due to saturation of conjugate-formation pathways. Decreases were observed for hexobarbital sleep times following 3-day treatment with 50 mg/kg of each of the test compounds and, consistent with hepatomegaly observed in subchronic studies, suggest induction of hepatic microsomal enzymes. The study supports evidence that these chemicals are cleared primarily via the urine in a dose-dependent manner, and are conjugated to water-soluble metabolites in both rats and rhesus monkeys.

p-Chlorophenyl Methyl Sulfide, p-Chlorophenyl Methyl Sulfoxide, and p-Chlorophenyl Methyl Sulfone. II. Subchronic Effects in Rodents and Rhesus Monkeys

1993 ◽  
Vol 12 (4) ◽  
pp. 377-395 ◽  
Author(s):  
Daryl C. Thake ◽  
Dennis C. Mays ◽  
A. Philip Leber ◽  
Jack C. Dacre
Keyword(s):  
Rhesus Monkeys ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Recovery Phase ◽  
Exposure Level ◽  
Cell Hyperplasia ◽  
Methyl Sulfide ◽  
Methyl Sulfoxide ◽  
Serum Blood Urea Nitrogen ◽  
Cns Depression

Rats, mice, and rhesus monkeys were subjected in subchronic exposures to the chemicals p-chlorophenyl methyl sulfide, p-chlorophenyl methyl sulfoxide, and p-chlorophenyl sulfone. Ninety-one-day toxicity studies were conducted by administering test chemicals to rodents at dietary concentrations of 750, 1500, and 3000 ppm. Clinical signs observed included transient central nervous system (CNS) depression, anorexia, and depressed weight gains. Minor alterations of hematologic and clinical chemistry parameters were also present. Gross and microscopic tissue findings in mice and rats included enlargement, necrotic and megalocytic changes of the liver. Damage to bronchiolar epithelium was observed in mice only at the highest exposure level. A 14-day gavage study in monkeys used daily dosages ranging from 2.5 to 80 mg/kg with an additional 15 days allotted for a recovery phase in one-half the test animals. Compound-related findings included lethality, CNS depression, and emesis. There were no significant compound-induced alterations in electrocardiographic or ophthalmic parameters. Serum blood urea nitrogen and serum glutamic pyruvic transaminase values were elevated in the highest dosage groups for the three test materials concomitant with increases in liver and kidney weights. Microscopic lesions included proliferative changes in lymph nodes, spleen, and bone marrow; hepatocellular vacuolization, degeneration, and necrosis; thyroid follicular cell hyperplasia; and degenerative lesions in gastric and intestinal epithelium. No-observable-effect levels (NOELs) were not established for any of the three test chemicals in the species tested.

Pharmacognostical Standardization and Pharmacological Potential of Elaeocarpus ganitrus Leaves as an Antiulcer Agent

2018 ◽  
Vol 11 (4) ◽  
pp. 4162-4169
Author(s):  
Mayank Kulshreshtha ◽  
Manjul Pratap Singh
Keyword(s):  
Skin Diseases ◽  
Scientific Data ◽  
Water Soluble ◽  
Histopathological Analysis ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Biochemical Studies ◽  
Pharmacological Potential ◽  
Dose Dependent

Elaeocarpus ganitrus Roxb, (E. ganitrus) known as Rudraksha belongs to family- Eleocarpaceae. It has a reflecting position in Hinduism and Ayurveda whereas traditionally it has mentioned to cure various health problems like fever, skin diseases, mental problems, wound healing etc. The present study was designed to study the microscopic and macroscopic analysis, physiochemical parameters, quantitative microscopy, phytochemical screening of E. ganitrus leaves as per WHO guidelines and evaluate the antiulcer potential of aqueous extract of E. ganitrus (AEEG) and ethanolic extract of E. ganitrus (EEEG) at the doses of 200 mg/kg and 400 mg/kg using pylorus ligation induced ulcers model, biochemical parameters. Hepatic, cardiac, hematological parameters have also done to find out the effect of different extracts on other major organs. Microscopic analysis proved the presence of covering trichomes, upper epidermis, lower epidermis, stomata, phloem, xylem etc. Ash value, water soluble ash, acid soluble ash, water soluble extract, alcohol soluble extract, loss on drying, swelling index, foaming index found to be 4.3 ± 0.52, 0.2 ± 0.33, 2.0 ± 0.2, 13.7 ± 0.25, 12.5 ± 0.55, 9.8 ± 0.23, 3.6 ± 0.04, more than 100. Different quantitative parameters were found out. Phytochemical analysis of different extracts showed the presence of various primary and secondary metabolite like alkaloids, glycosides, tannin, phenolic compounds etc. Pharmacological potential showed that extracts treated, and sucralfate treated groups showed significantly decreases in ulcer index in all above-mentioned models, biochemical studies clearly showed significant decreases in volume, pH, free acidity, total acidity of gastric content and increases in gastric mucus parameters like protein, total hexoses, hexosamine, fucose, sialic acid and DNA level. The level of antioxidant enzymes like LPO (Lipid peroxidation), SOD (Superoxide dimutase) were decreased and CAT (Catalase) level was increased. Level of PC (Plasma corticosterone) was decreased. Hematological, hepatic, cardiac parameters found to be normal during extracts treatment. Histopathological analysis clearly supports the biochemical studies at various doses and it was found to be effective in dose dependent manner. The obtained scientific data may be helpful to prepare the monograph of the plant and E. ganitrus has antiulcer potential in a dose dependent. Detailed study needed for better exposure of plant.

Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  
Keyword(s):  
Growth Rate ◽  
Lithium Treatment ◽  
Lithium Carbonate ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Blood Levels ◽  
Vaginal Mucosa ◽  
Dependent Manner ◽  
Serum Concentrations ◽  
Dose Dependent

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

Activation of Selective Transcription Factors and Cytokines by Water-Soluble Extract from Lentinus lepideus

2003 ◽  
Vol 228 (6) ◽  
pp. 749-758 ◽  
Author(s):  
Mirim Jin ◽  
Hyung Jin Jung ◽  
Jeong June Choi ◽  
Hyang Jeon ◽  
Jin Hwan Oh ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Post Treatment ◽  
Water Soluble ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Transient Transfection Assay ◽  
Gm Csf ◽  
Tnf Α ◽  
Water Soluble Extract

We isolated a water-soluble extract, PG101, from cultured mycelia of Lentinus lepideus. Treatment of human peripheral blood mononuclear cells (PBMCs) with PG101 increased levels of TNF-α, IL-1β, IL-10, and IL-12 by 100- to 1000-fold, whereas GM-CSF and IL-18 were activated by an order of magnitude. On the contrary, IFN-γ and IL-4 were not affected. The response to PG101 occurred in a dose- and time-dependent manner. From the human PBMCs treated with PG101, TNF-α was a first cytokine to be activated, detectable at 2 hr post-treatment followed by IL-1β at 6 hr post-treatment. IL-12 and IL-10 were the next to follow. GM-CSF and IL-18 both showed significant increases 24 hr after treatment. When PBMCs were sorted into various cell types, monocyte/macrophages, but not T and B cells, were the major target cell type responsive to PG101. Consistent with this result, the profile of cytokine expression upon PG101 treatment was comparable between PBMCs and a human promonocytic cell line (U937), whereas cell lines of T cell and myeloid origins did not respond to PG101. Data from a transient transfection assay involving specific reporter plasmids indicated that cellular transcription factor such as NF-κB, but not AP-1, was highly activated by PG101. Results from a gel retardation assay and the experiment involving a specific NF-κB inhibitor confirmed the involvement of NF-κB. Despite its significant biological effect on various cytokines, PG101 remained nontoxic in both rats and PBMCs even at a biological concentration approximately 20 times greater. PG101 demonstrates great potential as a therapeutic immune modulator.

scholarly journals Study on the Sleep-Improvement Effects of Hemerocallis citrina Baroni in Drosophila melanogaster and Targeted Screening to Identify Its Active Components and Mechanism

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 883
Author(s):  
Yuxuan Liang ◽  
Riming Huang ◽  
Yongchun Chen ◽  
Jing Zhong ◽  
Jie Deng ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
High Resolution Mass Spectrometry ◽  
Sleep Time ◽  
Network Pharmacology ◽  
Dependent Manner ◽  
Bioactive Components ◽  
Active Components ◽  
Edible Plant ◽  
Hemerocallis Citrina ◽  
Ultrahigh Performance Liquid Chromatography

Hemerocallis citrina Baroni (HC) is an edible plant in Asia, and it has been traditionally used for sleep-improvement. However, the bioactive components and mechanism of HC in sleep-improvement are still unclear. In this study, the sleep-improvement effect of HC hydroalcoholic extract was investigated based on a caffeine-induced insomnia model in Drosophila melanogaster (D. melanogaster), and the ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI-Orbitrap-MS) and network pharmacology strategy were further combined to screen systematically the active constituents and mechanism of HC in sleep-improvement. The results suggested HC effectively regulated the number of nighttime activities and total sleep time of D. melanogaster in a dose-dependent manner and positively regulated the sleep bouts and sleep duration of D. melanogaster. The target screening suggested that quercetin, luteolin, kaempferol, caffeic acid, and nicotinic acid were the main bioactive components of HC in sleep-improvements. Moreover, the core targets (Akt1, Cat, Ple, and Sod) affected by HC were verified by the expression of the mRNA of D. melanogaster. In summary, this study showed that HC could effectively regulate the sleep of D. melanogaster and further clarifies the multi-component and multi-target features of HC in sleep-improvement, which provides a new insight for the research and utilization of HC.

Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta)

1990 ◽  
Vol 122 (1) ◽  
pp. 96-100 ◽  
Author(s):  
Ulrich Fingscheidt ◽  
Gerhard F. Weinbauer ◽  
Shafiq A. Khan ◽  
Eberhard Nieschlag
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Rhesus Monkeys ◽  
Follicle Stimulating Hormone ◽  
Serum Levels ◽  
Lag Time ◽  
Dependent Manner ◽  
Control Serum ◽  
Dose Dependent ◽  
Stimulating Hormone

Abstract. Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

Chimera of Dimethylene Sulfone-, Methyl Sulfide-, and Methyl Sulfoxide-Linked Ribonucleotides and DNA

1996 ◽  
Vol 61 (21) ◽  
pp. 7620-7626 ◽  
Author(s):  
Daniel K. Baeschlin ◽  
Birgitte Hyrup ◽  
Steven A. Benner ◽  
Clemens Richert
Keyword(s):  
Methyl Sulfide ◽  
Methyl Sulfoxide

scholarly journals Quantification of Allyl Methyl Sulfide, Allyl Methyl Sulfoxide, and Allyl Methyl Sulfone in Human Milk and Urine After Ingestion of Cooked and Roasted Garlic

2020 ◽  
Vol 7 ◽  
Author(s):  
Wen Qin ◽  
Katrin Huber ◽  
Moritz Popp ◽  
Patrick Bauer ◽  
Andrea Buettner ◽  
...  
Keyword(s):  
Human Milk ◽  
Methyl Sulfide ◽  
Methyl Sulfoxide

scholarly journals Immunomodulatory Effects of a Low-Molecular Weight Polysaccharide from Enteromorpha prolifera on RAW 264.7 Macrophages and Cyclophosphamide- Induced Immunosuppression Mouse Models

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 340
Author(s):  
Yingjuan Liu ◽  
Xiaolin Wu ◽  
Weihua Jin ◽  
Yunliang Guo
Keyword(s):  
Mouse Models ◽  
The Body ◽  
Water Soluble ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Enteromorpha Prolifera ◽  
Immunomodulatory Effects ◽  
Raw 264.7 Macrophages ◽  
Cell Counts ◽  
Tnf Α

The water-soluble polysaccharide EP2, from Enteromorpha prolifera, belongs to the group of polysaccharides known as glucuronoxylorhamnan, which mainly contains glucuronic acid (GlcA), xylose (Xyl), and rhamnose (Rha). The aim of this study was to detect the immunomodulatory effects of EP2 on RAW 264.7 macrophages and cyclophosphamide (CYP)-induced immunosuppression mouse models. The cells were treated with EP2 for different time periods (0, 0.5, 1, 3, and 6 h). The results showed that EP2 promoted nitric oxide production and up-regulated the expression of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in a time-dependent manner. Furthermore, we found that EP2-activated iNOS, COX2, and NLRP3 inflammasomes, and the TLR4/MAPK/NF-κB signaling pathway played an important role. Moreover, EP2 significantly increased the body weight, spleen index, thymus index, inflammatory cell counts, and the levels of IL-1β, IL-6, and TNF-α in CYP-induced immunosuppression mouse models. These results indicate that EP2 might be a potential immunomodulatory drug and provide the scientific basis for the comprehensive utilization and evaluation of E. prolifera in future applications.

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