scholarly journals Evaluating the effect of Ganoderma lucidum polysaccharides on five cytochrome P450 isozymes with cocktail probe drugs in rats by LC–MS/MS

2019 ◽  
Vol 4 (1) ◽  
Keyword(s):  
Cytochrome P450 ◽  
Ganoderma Lucidum ◽  
Low Dose ◽  
Antioxidant Activities ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Positive Effects ◽  
Ganoderma Lucidum Polysaccharides ◽  
Tandem Mass Spectrometric

Ganoderma lucidum polysaccharides (GLPs) are commonly used as health-promoting medicine and dietary supplement due to the positive effects in immune modulation, antitumor and antioxidant activities. However, whether GLPs executes other uncharacterized effects is largely unclear. The rats were pre-primed with GLPs and then administrated with canonical “cocktail probes” of cytochrome P450 (CYP450) isozymes including caffeine, tolbutamide, dextromethorphan, omeprazole, and midazolam. The plasma concentrations of probes at each indicated time point were simultaneously detected using the designed high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. The results suggested that GLPs could increase the accumulated levels of caffeine, tolbutamide and midazolam in plasma as compared to control group. Besides, GLPs reduced the concentration of dextromethorphan in blood at high dose, while elevated it at low dose. GLPs could inhibit the activities of CYP1A2, and CYP3A4, additionally; GLPs at low dose suppressed the activity of CYP2D6, which demonstrated that drugs co-administrated with GLPs might require strictly evaluating the dose relation.

Effect of human recombinant superoxide dismutase on canine myocardial infarction

1990 ◽  
Vol 258 (2) ◽  
pp. H369-H380 ◽  
Author(s):  
B. S. Patel ◽  
M. O. Jeroudi ◽  
P. G. O'Neill ◽  
R. Roberts ◽  
R. Bolli
Keyword(s):  
Superoxide Dismutase ◽  
Infarct Size ◽  
Low Dose ◽  
Coronary Occlusion ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Collateral Flow ◽  
Tetrazolium Chloride ◽  
Arterial Blood

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) “low-dose” h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) “high-dose” h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

scholarly journals The Effects of Formaldehyde on Cytochrome P450 Isoform Activity in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Min Xu ◽  
Huaqiao Tang ◽  
Qian Rong ◽  
Yuanli Zhang ◽  
Yinglun Li ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
High Dose ◽  
Blood Samples ◽  
Time Points ◽  
Indoor Pollutant ◽  
Carcinogenic Effects

Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days). A mixture of the four probe drugs was injected into rats and blood samples were taken at a series of time points. Plasma concentrations of the probe drugs were measured by HPLC. The pharmacokinetic parameters t1/2, AUC(0-t), and Cmax of tolbutamide, chlorzoxazone, and testosterone increased significantly in the high dose versus control group (P<0.05), whereas the CL of chlorzoxazone and testosterone decreased significantly (P<0.05). However, t1/2, AUC(0-t), and Cmax of phenacetin decreased significantly (P<0.05), whereas the CL of phenacetin increased significantly (P<0.05) compared to controls. Thus, acute FA poisoning suppressed the activities of CYP2C11, CYP2E1, and CYP3A2 and induced the activity of CYP1A2 in rats. And the change of CYP450 activity caused by acute FA poisoning may be associated with FA potential carcinogenic effects on the airways.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

scholarly journals Low-dose sublingual immunotherapy compared to subcutaneous immunotherapy and conventional therapy in childhood asthma

2016 ◽  
Vol 44 (6) ◽  
pp. 243
Author(s):  
Ariyanto Harsono
Keyword(s):  
Childhood Asthma ◽  
Low Dose ◽  
Sublingual Immunotherapy ◽  
Disease Onset ◽  
Ethics Committee ◽  
Subcutaneous Immunotherapy ◽  
Control Group ◽  
High Dose ◽  
Treat Ment ◽  
Group A

Background Evidence begin to accumulate that high-dose sub-lingual immunotherapy (SLIT) is as effective as subcutaneousimmunotherapy (SIT) in the treatment of childhood asthma.Since the capacity of sublingual area is similar whether the doseis high or low, the efficacy of low dose may be important to bestudied.Objective To investigate the efficacy of low-dose sublingual im-munotherapy in the treatment of childhood asthma.Methods Parents signed informed consent prior to enrollment,after having received information about the study. Patients weremoderate asthma aged 6-14 years with disease onset of lessthan 2 years before the commencement of the study and peakexpiratory flow rate (PEFR) variability of more than 15%. Pa-tients were randomly allocated into group A, B, and C whoreceived subcutaneous immunotherapy, low-dose sublingualimmunotherapy, and conventional asthma therapy, respectively.Randomization was stratified into two strata according to agei.e., 6-11 years or 11-14 years. Patients of each stratum wererandomized in block of three for each group. At the end of threemonths, lung function tests were repeated. The primary outcomewas PEFR variability at the end of the study. The study wasapproved by the Ethics Committee of Soetomo HospitalSurabaya.Results Distribution of variants as represented by sex, age,eosinophil count, and total IgE concentration were normal inthe three groups. PEFR variability decreased significantly from16.97+0.81 to 8.50+5.08 and 17.0+0.87 to 8.40+4.72 in groupreceiving SIT and SLIT, respectively (p<0.05), but decreasednot significantly from 17.00+0.83 to 10.82+0.5.41 in control group(p>0.05).Conclusion Low-dose SLIT is as efficacious as SIT in the treat-ment of moderate asthma in children

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

2016 ◽  
Vol 9 (5) ◽  
pp. 197
Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  
Keyword(s):  
Liver Function ◽  
Toxicity Test ◽  
Low Dose ◽  
Ethanol Extract ◽  
Good Effect ◽  
Control Group ◽  
High Dose ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

scholarly journals Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangui Zhao ◽  
Wenjun Wang
Keyword(s):  
Ovarian Reserve ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Menopausal Syndrome ◽  
Primordial Follicles ◽  
Akt Phosphorylation ◽  
Vinylcyclohexene Diepoxide ◽  
Sd Rats

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.

scholarly journals Quantitation, Absorption and Tissue Distribution of Coenzyme Q10 from Pak-wanban (Sauropus androgynus L. Merr.) Leaf and Its Antioxidant Activities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Aikkarach KETTAWAN ◽  
Kansuda WUNJUNTUK
Keyword(s):  
Tissue Distribution ◽  
Coenzyme Q10 ◽  
Antioxidant Activities ◽  
Alpha Tocopherol ◽  
Control Group ◽  
High Dose ◽  
Cooking Oil ◽  
Supplement Group ◽  
Male Wistar Rats ◽  
Plasma Antioxidant

Pak-wanban (Sauropus androgynus L. Merr.), a popular Thai vegetable, has been found to have a high content of Coenzyme Q10 (CoQ10), which is a powerful antioxidant. This study investigated the quantitation, absorption and tissue distribution of CoQ10 from raw and stir-fried Pak-wanban and its antioxidant activities in rats. Male Wistar rats (seven weeks old) were randomly grouped as follows: (1) control, (2) raw Pak-wanban powder of 0.5 mg CoQ10/kg/day, (3) stir-fried Pak-wanban powder of 0.5 mg CoQ10/kg/day, (4) stir-fried Pak-wanban powder of 1.0 mg CoQ10/kg/day, and (5) commercially CoQ10 supplement groups of 0.5 mg CoQ10/kg/day. The results found that stir-fried cooking did not significantly reduce the content of CoQ10 in the Pak-wanban leaves. After 3 weeks of experimentation, the level of CoQ10 in the plasma, liver and spleen was increased in all Pak-wanban groups when compared to the control group. The level of CoQ10 in the stir-fried Pak-wanban group was significantly higher than the raw Pak-wanban group but slightly lower than the CoQ10 supplement group.  Liver alpha-tocopherol concentrations were markedly increased in rats that consumed a high dose of CoQ10 from stir-fried Pak-wanban of 1 mg of CoQ10/kg/day when compared with the control group. Plasma antioxidant activities (ORAC: FRAP: DPPH) were significantly increased in both groups of stir-fried Pak-wanban when compared with the control group. We concluded that CoQ10 in  Pak-wanban could be well absorbed and improved the plasma antioxidant activities. Furthermore, cooking oil may increase the bioavailability of CoQ10 from vegetables. Therefore, it would be useful for vegetarian people.

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