Inhibitory Effect of Tetrandrine on Pulmonary Metastases in CT26 Colorectal Adenocarcinoma–Bearing BALB/c Mice

2004 ◽  
Vol 32 (06) ◽  
pp. 863-872 ◽  
Author(s):  
Kou-Hwa Chang ◽  
Hui-Fen Liao ◽  
Hen-Hong Chang ◽  
Yu-Yawn Chen ◽  
Ming-Chien Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Body Weight ◽  
Tumor Metastasis ◽  
Colorectal Adenocarcinoma ◽  
Pulmonary Metastases ◽  
Inhibitory Effect ◽  
Control Group ◽  
Dependent Manner ◽  
Untreated Control Group ◽  
Dose Dependent

Tumor metastasis is a major cause of mortality in cancer patients. The anti-metastatic effect of tetrandrine, an alkaloid isolated from Stephania tetrandrae S. Moore, was investigated in a pulmonary metastatic model of colorectal cancer-bearing mice. Tetrandrine decreased the viability of murine colorectal adenocarcinoma CT26 cells in a time- and dose-dependent manner. CT26 cells were injected into BALB/c mice via a tail vein to establish pulmonary metastases. After this, the mice were given intraperitoneal injections of tetrandrine (10 mg/kg/day), 5-fluorouracil (5-FU) at the same dose, or vehicle for 5 consecutive days. Mice treated with tetrandrine had 40.3% fewer metastases than vehicle-treated mice, and those treated with 5-FU had 36.9% fewer metastases than controls. Both tetrandrine- and 5-FU-treated mice survived longer than mice in the untreated control group. There was no acute toxicity or obvious changes in body weight in any of the mice. These results suggest that tetrandrine may be a useful anti-metastatic agent.

scholarly journals Neurotoxic effect in lactating mice pups received oseltamivir phosphate (tamiflu) through milk from dosed nursing mothers during lactation period

2012 ◽  
Vol 36 (1) ◽  
pp. 75-84
Author(s):  
Areej B. Abass
Keyword(s):  
Body Weight ◽  
Clinical Symptoms ◽  
Body Weight Gain ◽  
Control Group ◽  
Lactation Period ◽  
Dependent Manner ◽  
Neurotoxic Effect ◽  
Nursing Mothers ◽  
Oseltamivir Phosphate ◽  
Dose Dependent

The present study was aimed to evaluate neurotoxic effects of oseltamivir phosphate in lactating pups of orally dosed mice mothers during lactation. Twelve recently parturited female albino mice were divided equally into three groups, one control and two treated groups, each group consists of 4 dosed dams and 8 chosen pups .The nursing dams of T1 and T2 dosed daily orally with 1mg/kg and 5mg/kg,oseltamivir phosphate respectively representing the therapeutic dose and 5 fold dose of drug while control group dosed with distilled water. Lactating mice pups of all groups examined for the following parameters: First parameter was body weight changes and gain: In which T1group showed significant increase in mice pups body weight gain after 14 day of treatment in comparison with control group and T2. Second parameter was clinical symptoms observation /daily, all treatment groups that showed neurotoxic symptoms appeared from 1st dose and extended along the next few days of treatment to be gradually disappeared and completely lost within the last days of treatment in dose dependent manner.These neurotoxic symptoms were weakness, convulsions ,lay on back or side, extended body, incoordination ,extended limbs and limbs stiffness. Third parameter was gross and histopathological studies which demonstrate that the brain was the most affected organ beside extensive lesions in liver, kidney, stomach and small intestine of treated groups in dose dependent manner.In conclusion of this study revealed that Oseltamivir phosphate produce neurotoxic effect in mice pups through indirect administration by nursing mothers dosing during lactation period and the level of toxicity was in dose dependent manner.

scholarly journals Studies of Anti-arrhythmic and Hypercholesterolemic Activities of Ayurvedic Preparation ‘Lauhasab’ in Rat Model

2017 ◽  
Vol 16 (1) ◽  
pp. 95-105
Author(s):  
Refaya Rezwan ◽  
Sharmin Zafar ◽  
Abu Asad Chowdhury ◽  
Shaila Kabir ◽  
Mohammad Shah Amran ◽  
...  
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Cardiovascular Diseases ◽  
Animal Experiments ◽  
Control Group ◽  
Dependent Manner ◽  
Pharmacological Activities ◽  
Delayed Onset ◽  
Dose Dependent ◽  
Mean Heart Rate

Lauhasab, an Ayurvedic preparation, is widely used in anemia and cardiovascular diseases. Despite its claim as a cardio-tonic there is paucity of studies on pharmacological activities and toxicities. In this study, the anti-arrhythmic effect and impact on lipid profile were evaluated. Rats were pretreated with 0.28 and 2.8 ml/kg body weight of Lauhasab for 35 days and electrocardiographic tracings were recorded and analyzed to determine heart rate and occurrence of arrhythmia. Electrocardiogram recorded before digoxin administration showed significant decrease in mean heart rate along with longer duration of bradycardia than in digoxin control group after 35 days of chronic pretreatment with both doses of Lauhasab. In animal experiments, various arrhythmias were observed after intraperitoneal injection of digoxin. Lauhasab decreased the duration and delayed onset of time of various arrhythmias. It showed significant increase in cholesterol and triglyceride levels in a dose dependent manner. It can be concluded that Lauhasab possesses significant anti-arrhythmic activity against digoxin-induced arrhythmia. It also revealed hyperlipidemic effects.Dhaka Univ. J. Pharm. Sci. 16(1): 95-105, 2017 (June)

scholarly journals A Metabolic Profiling Study of Realgar-Induced Acute Kidney Injury in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Zhang ◽  
Chao Li ◽  
Tingting Feng ◽  
Shuai Cao ◽  
Heng Zhou ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Body Weight ◽  
Correlation Analysis ◽  
Metabolic Profiling ◽  
Kidney Injury ◽  
Control Group ◽  
Dependent Manner ◽  
Kidney Weight ◽  
Dose Dependent ◽  
Metabolomic Approach

Realgar has been used as a type of mineral drug that contains arsenic for thousands of years. Previous studies have shown that Realgar-induced acute kidney injury is associated with abnormal metabolism, but the underlying mechanism is poorly understood. The aim of this study is to investigate the metabolic changes in serum and kidney tissues of mice exposed to Realgar by using a metabolomic approach and explore the molecular mechanisms of acute kidney injury induced by Realgar. Forty mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After 1 week, the body weight and kidney weight of the mice were measured. The serum and kidney samples were used for LC-MS spectroscopic metabolic profiling. Principal component analysis (PCA), correlation analysis, and pathway analysis were used to detect the nephrotoxic effects of Realgar. Body weight decreased significantly in the 2.0 g/kg group, and the kidney weight index also showed a dose-dependent increase in Realgar. The PCA score plot showed the serum and kidney tissue metabolic profile of mice exposed to 2.0 g/kg Realgar separated from the control group, while the lower-doses of 0.5 g/kg and 1.0 g/kg Realgar shown a similar view to the Control group. Thirty-three metabolites and seventeen metabolites were screened and identified in the serum and kidney of mice in a dose-dependent manner. respectively. Correlation analysis showed a strong correlation among these metabolites. Amino acid metabolism, lipid metabolism, glutathione metabolism, and purine metabolism pathways were found to be mainly associated with Realgar nephrotoxicity. This work illustrated the metabolic alterations in Realgar-induced nephrotoxic mice through a metabolomic approach.

Studies on Apoptosis and Mechanism of Curcumin Chitosan Induced Human Colon Cancer Cells in Colorectal Cancer

2020 ◽  
Vol 10 (7) ◽  
pp. 987-991
Author(s):  
Quanlan Wang ◽  
Peng Liao ◽  
Yinglin Wu ◽  
Yuanhua Huang ◽  
Yan Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Flow Cytometry ◽  
Annexin V ◽  
Human Colon ◽  
Optical Microscope ◽  
Inhibitory Effect ◽  
Control Group ◽  
Dependent Manner ◽  
Human Colon Cancer ◽  
Ht29 Cells

To explore the function of curcumin chitosan on the proliferation of human colorectal cancer HT29 cells and to explore its effect on apoptosis. We applied MTT assay to test the inhibitory effect of curcumin chitosan on the proliferation of HT29 cells. The alterations of colorectal cancer cell morphology were observed by optical microscope and electron microscope. The change of early apoptosis rate was determined by flow cytometry using Annexin-V/PI double staining. By Comparison with the control group, curcumin chitosan significantly suppressed the cell proliferation and promoted cell apoptosis of HT29 cells in not only dose- but also time-dependent manner; through light microscopy and electron microscopy, the cell volume was reduced, the cell membrane was shrunk, chromatin was significantly concentrated. Typical apoptotic features such as aggregation; flow cytometry confirmed a significant increase in apoptotic rates (p < 0 05).

Eclipta alba ameliorates carbon tetrachloride-induced structural and functional changes in liver of mice

2013 ◽  
Vol 1 (1) ◽  
pp. 112
Author(s):  
Monali R. Patel ◽  
Ramtej J. Verma
Keyword(s):  
Lipid Peroxidation ◽  
Body Weight ◽  
Carbon Tetrachloride ◽  
Fatty Infiltration ◽  
Control Group ◽  
Dependent Manner ◽  
Histopathological Changes ◽  
Functional Changes ◽  
Eclipta Alba ◽  
Dose Dependent

The aim of the present investigation was to evaluate the ameliorative effect of Eclipta alba extract against carbon tetrachloride (CCl4)–induced structural and functional changes in livers of mice. Healthy adult Swiss strain female albino mice were orally administered with CCl4 (826 mg/kg body weight/day, p.o.) alone and along with Eclipta alba extract (100, 200 and 300 mg/kg body weight/day, p.o.) for 30 days. The degree of protection was determined by measuring histopathological changes and lipid peroxidation in liver as well as activities of ALT, AST, ACP, ALP, LDH, γ-GT enzymes and bilirubin contents in serum of mice. The histopathological studies revealed severe necrosis, fatty infiltration, lymphocytic infiltration and fibrosis in liver of CCl4 treated mice. In addition, biochemical studies revealed a significant increase in lipid peroxidation. The enzymes activities as well as bilirubin contents in serum were significantly (p<0.05) increased in CCl4 only treated mice when compared with the control group. However, co-treatment of CCl4 along with Eclipta alba extract showed significant reductions in activities of enzymes and bilirubin content as compared with CCl4 alone treated mice. The effects were dose-dependent (r = 0.9826 to 1). Carbon tetrachloride induced lipid peroxidation was significantly (p<0.05) ameliorated in a dose-dependent manner. Histopathological changes were also ameliorated on treatment with Eclipta alba extract. The ameliorative effects of Eclipta alba on CCl4–induced hepatotoxicity could be due to its antioxidative property. The extract was found to be safe as evidenced by their high LD50.

Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

2018 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Xiaofeng Bao ◽  
Ying Xue ◽  
Chao Xia ◽  
Yin Lu ◽  
Ningjing Yang ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Iron Starvation ◽  
Hydrochloride Salt ◽  
Obligate Intracellular ◽  
Biphasic Life Cycle ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Dose Dependent ◽  
Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

scholarly journals Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer

2021 ◽  
Vol 38 (2) ◽  
Author(s):  
Wenqian Zheng ◽  
Jinhui Hu ◽  
Yiming Lv ◽  
Bingjun Bai ◽  
Lina Shan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

AbstractThe use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

scholarly journals Effect of lemon peel flavonoids on anti-fatigue and anti-oxidation capacities of exhaustive exercise mice

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Guili Bao ◽  
Yinglong Zhang ◽  
Xiaoguang Yang
Keyword(s):  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Fatty Acid Content ◽  
Hepatic Tissue ◽  
Control Group ◽  
Dependent Manner ◽  
Lemon Peel ◽  
Tnf Α ◽  
Dose Dependent

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.

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