scholarly journals Influences of Anlotinib on Cytochrome P450 Enzymes in Rats Using a Cocktail Method

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Sun ◽  
Zhe Wang ◽  
Ruimin Chen ◽  
Chengke Huang ◽  
Rui Sun ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oral Administration ◽  
Inductive Effect ◽  
Saline Control ◽  
Control Group ◽  
Cytochrome P450 Enzymes ◽  
Saline Control Group ◽  
Blood Samples ◽  
Time Points

The present study aimed to investigate the effect of anlotinib (AL3818) on pharmacokinetics of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C6, CYP2D1, CYP2D2, and CYP3A1/2) by using five cocktail probe drugs in vivo. After pretreatment for 7 days with anlotinib (treatment group) or saline (control group) by oral administration, probe drugs phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam were administered to rats by oral administration. Blood samples were obtained at a series of time-points and the concentrations of five probe drugs in plasma were determined by a UHPLC-MS/MS method. The results showed that treatment with anlotinib had no significant effect on rat CYP1A2, CYP2D2, and CYP2C6. However, anlotinib had a significant inductive effect on CYP2D1 and CYP3A1/2. Therefore, caution is needed during the concomitant use of anlotinib with other drugs metabolized by CYP2D1 and CYP3A1/2 because of potential drug-anlotinib interactions.

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.

scholarly journals Effects of intravenous infusion of E.coli lipopolysaccharide in early pregnant cows

Reproduction ◽  
2018 ◽  
Author(s):  
Kathrin Herzog ◽  
Letizia Debertolis ◽  
John P Kastelic ◽  
Marion Schmicke ◽  
Susanne E Ulbrich ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Blood Flow ◽  
Saline Control ◽  
Control Group ◽  
Saline Control Group ◽  
Blood Samples ◽  
Luteal Tissue ◽  
Embryonic Loss ◽  
Pre Treatment ◽  
Embryonic Viability

The objective was to characterize effects of Escherichia coli LPS (given iv) on corpus luteum (CL) and embryonic viability in early pregnant cattle. Eight non-lactating German Holstein cows were given 0.5 µg/kg LPS on 35 ± 3 d (mean ± SEM) of pregnancy, whereas seven heifers, 41 ± 6 d pregnant, were given 10 ml saline (Control group). Transrectal B-mode examinations of the CL were done at -1, 3, 6, 12, 24, 48, 72, and 96 h relative to treatment. Blood samples were collected at -1, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 48, 72, and 96 h. At 12 and 48 h, the CL was biopsied. None of the cows still in the experiment 10 d after LPS (n=7) had embryonic loss. In LPS-treated cows, luteal area decreased (from 4.1 to 3.1 cm2; P≤0.05) within 6 h and until 48 h. Luteal blood flow decreased by 39% (P≤0.05) within the first 6 h after LPS, but returned to pre-treatment values by 48 h. Plasma P4 decreased by 62% (P≤0.05), reached a nadir (2.7±0.6 ng/mL) at 12 h after LPS and was not restored to pre-treatment (P≤0.05). In luteal tissue, mRNAs for StAR and for FGF1 were lower (P≤0.05) in LPS- than in saline-treated cattle at 12 h, with no difference between groups at 48 h. Levels of mRNAs for Casp3 and FGF2 were not different between groups (P>0.05) at 12 or 48 h after treatment. In conclusion, LPS transiently suppressed CL function, but did not induce embryonic mortality.

scholarly journals Inhibitory effect of endostatin gene therapy combined with phosphorus-32 colloid on tumour growth in Wistar rats

2016 ◽  
Vol 36 (3) ◽  
Author(s):  
Huiqi Gao ◽  
Jing Zhu ◽  
Yong Li ◽  
Peng Fu ◽  
Baozhong Shen
Keyword(s):  
Wistar Rats ◽  
Tumour Growth ◽  
Combined Therapy ◽  
Inhibitory Effect ◽  
Saline Control ◽  
Control Group ◽  
Healthy Male ◽  
Saline Control Group ◽  
Male Wistar Rats

Eighty healthy male Wistar rats, aged 5 weeks, weighing 100–120 g, were utilized for establishing tumour-bearing models by immediate Walker-256 cancerous ascites injection and randomly divided to four groups (n=20) treated with 0.2 ml solution containing saline, 32P-colloid (0.3 mCi), endostatin gene (20 μg), endostatin gene combined with colloid 32P. The effect of endostatin combined with a small dose of 32P-colloidal on tumour growth in vivo was evaluated and the potential mechanism underlying the combined therapy was explored. We found that 32P-colloid combined with endostatin exhibited higher inhibitory effect upon tumour growth compared with application of 32P-colloid or endostatin alone, although three therapies all significantly inhibited tumour growth compared with saline control group. The higher inhibitory effect of 32P-colloid combined with endostatin upon tumour growth might be attributed to a synergistic effect of inhibiting angiogenesis by endostatin and inducing apoptosis by 32P-colloid, as demonstrated by microvessel density (MVD) and apoptotic index (AI) measurement. Combined therapy of 32P-colloid and endostatin probably serves as a novel and efficacious therapy of tumour growth.

scholarly journals Oral Glutamine Is Superior Than Oral Glucose to Promote Glycemia Recovery in Mice Submitted to Insulin-Induced Hypoglycemia

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Amanda Nunes Santiago ◽  
Vilma Aparecida Ferreira de Godoi-Gazola ◽  
Mariana Fachin Milani ◽  
Vanessa Cristina de Campos ◽  
Vanessa Rodrigues Vilela ◽  
...  
Keyword(s):  
Oral Administration ◽  
Glucose Production ◽  
Insulin Injection ◽  
Regular Insulin ◽  
Recovery Phase ◽  
Saline Control ◽  
Control Group ◽  
Oral Glucose ◽  
Saline Control Group ◽  
The Impact

The effect of the oral administration of blood glucose precursors on glycemia recovery and liver glucose production in fasted mice subjected to insulin-induced hypoglycemia (IIH) was investigated. IIH was obtained with increasing doses (from 0.5 to 2.0 U·kg−1) of intraperitoneal regular insulin where glycemia was evaluated from 0 to 300 min after insulin injection. The dose of 1.0 U·kg−1showed the best results, that is, a clear glycemia recovery phase without convulsions or deaths. Thus, this dose was used in all experiments. Afterwards, mice submitted to IIH received orally by gavage: saline (control group), glucose (100 mg·kg−1), glycerol (100 mg·kg−1), lactate (100 mg·kg−1), alanine (100 mg·kg−1), or glutamine (100 mg·kg−1). It was observed that glutamine was more effective in promoting glycemia recovery if compared with glucose, lactate, glycerol, or alanine. In agreement with these results, the best performance in terms of liver glucose production was obtained when glutamine was used as glucose precursors. These results open perspectives for clinical studies to investigate the impact of oral administration of gluconeogenic amino acids to promote glycemia recovery during hypoglycemia.

scholarly journals Enzymatic activity in turkey, duck, quail and chicken liver microsomes against four human cytochrome P450 prototype substrates and aflatoxin B1

2011 ◽  
Vol 1 (1) ◽  
pp. 4 ◽  
Author(s):  
Hansen W. Murcia ◽  
Gonzalo J. Díaz ◽  
Sandra Milena Cepeda
Keyword(s):  
Cytochrome P450 ◽  
Aflatoxin B1 ◽  
Enzyme Activities ◽  
High Performance ◽  
Biochemical Characterization ◽  
Liver Microsomes ◽  
Cytochrome P450 Enzymes ◽  
Catalytic Rate

Cytochrome P450 enzymes (CYP) are a group of monooxygenases able to biotransform several kinds of xenobiotics including aflatoxin B1 (AFB1), a highly toxic mycotoxin. These enzymes have been widely studied in humans and others mammals, but there is not enough information in commercial poultry species about their biochemical characteristics or substrate specificity. The aim of the present study was to identify CYPs from avian liver microsomes with the use of prototype substrates specific for human CYP enzymes and AFB1. Biochemical characterization was carried out in vitro and biotransformation products were detected by high-performance liquid chromatography (HPLC). Enzymatic constants were calculated and comparisons between turkey, duck, quail and chicken activities were done. The results demonstrate the presence of four avian ortholog enzyme activities possibly related with a CYP1A1, CYP1A2, CYP2A6 (activity not previously identified) and CYP3A4 poultry orthologs, respectively. Large differences in enzyme kinetics specific for prototype substrates were found among the poultry species studied. Turkey liver microsomes had the highest affinity and catalytic rate for AFB1 whereas chicken enzymes had the lowest affinity and catalytic rate for the same substrate. Quail and duck microsomes showed intermediate values. These results correlate well with the known in vivo sensitivity for AFB1 except for the duck. A high correlation coefficient between 7-ethoxyresorufin-Odeethylase (EROD) and 7-methoxyresorufin- O-deethylase (MROD) activities was found in the four poultry species, suggesting that these two enzymatic activities might be carried out by the same enzyme. The results of the present study indicate that four prototype enzyme activities are present in poultry liver microsomes, possibly related with the presence of three CYP avian orthologs. More studies are needed in order to further characterize these enzymes.

Addition of Epinephrine to Intrathecal Bupivacaine and Sufentanil for Ambulatory Labor Analgesia

1997 ◽  
Vol 86 (3) ◽  
pp. 525-531 ◽  
Author(s):  
David C. Campbell ◽  
Robert Banner ◽  
Lesley-Ann Crone ◽  
Wendy Gore-Hickman ◽  
Ray W. Yip
Keyword(s):  
Labor Analgesia ◽  
Saline Control ◽  
Control Group ◽  
Double Blind Study ◽  
Saline Control Group ◽  
Double Blind ◽  
Prolonged Labor ◽  
Intrathecal Analgesia ◽  
Limited Duration ◽  
Effective Analgesia

Background The intrathecal combination of sufentanil and bupivacaine provides rapid, effective analgesia for labor with a limited duration. Many anesthesiologists have concerns that the use of intrathecal local anesthetics precludes maternal ambulation. This prospective, randomized, double-blind study was designed to determine whether the addition of epinephrine to the combination of sufentanil and bupivacaine would prolong intrathecal analgesia for labor. Patients' ability to ambulate was also assessed. Methods Thirty-nine patients received either an intrathecal control dose of 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml normal saline (control group); or 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml (0.2 mg) of epinephrine (EPI group). Results Seven patients (3 control, 4 EPI) delivered vaginally and two (1 control, 1 EPI) required cesarean delivery before requesting epidural analgesia. The duration (mean +/- SD) of intrathecal labor analgesia was prolonged significantly by the addition of epinephrine: control (n = 15): 145 +/- 23 min; EPI (n = 15): 188 +/- 25 min (P &lt; 0.0001). Maternal ambulation was demonstrated in 100% (19 of 19) of the control group and in 80% (16 of 20) of the EPI group (P = NS). Conclusions The addition of 0.2 mg epinephrine to the intrathecal combination of sufentanil and bupivacaine significantly prolonged labor analgesia without causing adverse effects to the mother or fetus. The intrathecal combination of sufentanil and bupivacaine, with or without epinephrine, provided rapid, profound labor analgesia and allowed most patients to ambulate.

scholarly journals Acetylsalicylic acid and morphology of red blood cells

2010 ◽  
Vol 53 (3) ◽  
pp. 575-582 ◽  
Author(s):  
Jacques Natan Grinapel Frydman ◽  
Adenilson de Souza da Fonseca ◽  
Vanessa Câmara da Rocha ◽  
Monica Oliveira Benarroz ◽  
Gabrielle de Souza Rocha ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Control Group ◽  
Blood Samples ◽  
Morphological Alterations ◽  
Blood Smears ◽  
In Vivo Treatment ◽  
Microscopy Data

This work evaluated the effect of in vitro and in vivo treatment with ASA on the morphology of the red blood cells. Blood samples or Wistar rats were treated with ASA for one hour. Blood samples or animals treated with saline were used as control group. Blood smears were prepared, fixed, stained and the qualitative and quantitative morphology of red blood cells were evaluated under optical microscopy. Data showed that the in vitro treatment for one hour with ASA at higher dose used significantly (p<0.05) modified the perimeter/area ratio of the red blood cells. No morphological alterations were obtained with the in vivo treatment. ASA use at highest doses could interfere on shape of red blood cells.

scholarly journals Evaluation of the Effect of Hydroalcoholic Extracts of Cassia Occidentalis Leaves in Neutrophil Adhesion Test in Rats

2020 ◽  
Vol 9 (4-s) ◽  
pp. 1218-1221 ◽  
Author(s):  
Dhaval M Patel ◽  
Advaita B Patel ◽  
Riddhi D Trivedi ◽  
Viram J Parmar ◽  
Urvisha V Bangoriya
Keyword(s):  
Oral Administration ◽  
Leukocyte Count ◽  
Control Group ◽  
Neutrophil Adhesion ◽  
Adhesion Test ◽  
Differential Leukocyte Count ◽  
Hydroalcoholic Extract ◽  
Cassia Occidentalis ◽  
Blood Samples ◽  
Blood Smears

Evaluation of the effect of hydroalcoholic extracts of Cassia occidentalis leaves in neutrophil adhesion test in Rats. The effect of oral administration of hydroalcoholic extract of Cassia occidentalis leaves on neutrophil has been studied and is compared with control group on rats. The differential leukocyte count (DLC) was performed by fixing the blood smears and staining with leucofine and percent neutrophils in each sample was determined. After the initial counts, blood samples were incubated with 80 mg/ml of nylon fibers for 10 min at 37ºC. Supplementation with hydroalcoholic extract of Cassia occidentalis leaves significantly decreased neutrophil adhesion. The results indicate that the leaf of Cassia occidentalis is endowed with protected neutrophil adhesion. These effects could conclude that Cassia occidentalis has an antiasthmatic property. Keywords: Cassia occidentalis, Neutrophil adhesion, analysis of variance

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