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1.
Article in English | WPRIM | ID: wpr-929002

ABSTRACT

OBJECTIVES@#Nephrotic syndrome is a common disease of the urinary system. The aim of this study is to explore the effect of astragalus polysaccharides (APS) on multidrug resistance gene 1 (MDR1) and P-glycoprotein 170 (P-gp170) in adriamycin nephropathy rats and the underlying mechanisms.@*METHODS@#A total of 72 male Wistar rats were divided into a control group, a model group, an APS low-dose group, an APS high-dose group, an APS+micro RNA (miR)-16 antagomir group and an APS+miR-16 antagomir control group, with 12 rats in each group. Urine protein (UP) was detected by urine analyzer, and serum cholesterol (CHOL), albumin (ALB), blood urea nitrogen (BUN), and creatinine (SCr) were detected by automatic biochemical analyzer; serum interleukin-6 (IL-6), IL-1β, tumor necrosis factor α (TNF-α) levels were detected by ELISA kit; the morphological changes of kidney tissues were observed by HE staining; the levels of miR-16 and MDR1 mRNA in kidney tissues were detected by real-time RT-PCR; the expression levels of NF-κB p65, p-NF-κB p65, and P-gp170 protein in kidney tissues were detected by Western blotting; and dual luciferase was used to verify the relationship between miR-16 and NF-κB.@*RESULTS@#The renal tissue structure of rats in the control group was normal without inflammatory cell infiltration. The renal glomeruli of rats in the model group were mildly congested, capillary stenosis or occlusion, and inflammatory cell infiltration was obvious. The rats in the low-dose and high-dose APS groups had no obvious glomerular congestion, the proliferation of mesangial cells was significantly reduced, and the inflammatory cells were reduced. Compared with the high-dose APS group and the APS+miR-16 antagomir control group, there were more severe renal tissue structure damages in the APS + miR-16 antagomir group. Compared with the control group, the levels of UP, CHOL, BUN, SCr, IL-6, IL-1β, TNF-α, and MDR1 mRNA, and the protein levels of p-NF-κB p65 and P-gp170 in the model group were significantly increased (all P<0.05); the levels of ALB and miR-16 were significantly decreased (both P<0.05). Compared with the model group, the levels of UP, CHOL, BUN, SCr, IL-6, IL-1β, TNF-α, and MDR1 mRNA, and the protein levels of pNF-κB p65 and P-gp170 in the low-dose and high-dose APS groups were significant decreased (all P<0.05); and the levels of ALB and miR-16 were significantly increased (both P<0.05). Compared with APS+miR-16 antagomir control group, the UP, CHOL, BUN, SCr, IL-6, IL-1β, and TNF-α levels, MDR1 mRNA, and the protein levels of p-NF-κB p65 and P-gp170 were significantly increased (all P<0.05). The levels of ALB and miR-16 were significantly decreased in the APS+miR-16 antagomir group compared with the APS+miR-16 antagomir control group (both P<0.05).@*CONCLUSIONS@#APS can regulate the miR-16/NF-κB signaling pathway, thereby affecting the levels of MDR1 and P-gp170, and reducing the inflammation in the kidney tissues in the adriamycin nephropathy rats.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Animals , Antagomirs , Doxorubicin/toxicity , Genes, MDR , Interleukin-6/metabolism , Kidney Diseases/genetics , Male , MicroRNAs/metabolism , NF-kappa B/metabolism , Polysaccharides/pharmacology , RNA, Messenger , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism
2.
Article in Chinese | WPRIM | ID: wpr-928716

ABSTRACT

OBJECTIVE@#Two sgRNAs transfected FLT3-ITD+AML cell line MV411 with different binding sites were introduced into CRISPR/cas9 to obtain MV411 cells with miR-155 gene knockout. To compare the efficiency of miR-155 gene knockout by single and double sgRNA transfection and their effects on cell phenotypes.@*METHODS@#The lentiviral vectors were generated containing either single sgRNA or dual sgRNAs and packaged into lentivirus particles. PCR was conducted to measure gene editing efficiency, and miR-155 expression was evaluated by qPCR. CCK-8 assay was used to evaluate the cell proliferation, and calculate drug sensitivity of cells to adriamycin and quizartinib. Annexin V-APC/7-AAD staining was used to label cell apoptosis induced by adriamycin and quizartinib.@*RESULTS@#In the dual sgRNAs transfected cells, a cleavage band could be observed, meaning the success of gene editing. Compared with the single sgRNA transfected MV411 cells, the expression level of mature miR-155-5p was lower in the dual sgRNA transfected cells. And, dual sgRNA transfected MV411 were more sensitive to adriamycin and quizartinib with lower IC50 and higher apoptosis rate.@*CONCLUSION@#The inhibition rate of miR-155 gene expression transfected by dual sgRNA is higher than that by single sgRNA. Dual sgRNA transfection can inhibit cell proliferation, reverse drug resistance, and induce apoptosis more significantly. Compared with single sgRNA transfection, dual sgRNA transfection is a highly efficient gene editing scheme.


Subject(s)
CRISPR-Cas Systems , Doxorubicin/pharmacology , Drug Resistance , Gene Editing , Humans , Leukemia, Myeloid, Acute/genetics , MicroRNAs/genetics , RNA, Guide/genetics , fms-Like Tyrosine Kinase 3/genetics
3.
Article in Chinese | WPRIM | ID: wpr-923021

ABSTRACT

Objective To study the reversal effect of Shenfu decoction(SFD)on adriamycin-induced cardiomyopathy and explore its mechanism by using serum metabolomic technology. Methods The BALB/c mouse model of cardiomyopathy induced by adriamycin was established. The corresponding intervention was given. The serum lactate dehydrogenase(LDH)and creatine phosphatase isoenzyme MB(CK-MB)were measured. The ejection fraction (EF) and shortening fraction (FS) were measured by echocardiography. Mouse serum was collected for gas chromatography-mass spectrometry (GC-MS) analysis. The data obtained was analyzed by multivariate and univariate statistical analysis to compare the changes of endogenous metabolites in the serum of mice in the normal group, model group and Shenfu decoction treatment group, to find the potential biomarkers of Shenfu decoction to reverse the adriamycin-induced cardiomyopathy. Metabolic pathway analysis was used to explore the targeted metabolic pathway of Shenfu decoction. Results The levels of serum LDH and CK-MB in the model group were increased significantly, and the values of EF and FS decreased significantly, indicating that the model was successfully established. The above indicators were significantly improved after treatment with Shenfu decoction. 13 potential biomarkers of adriamycin-induced cardiomyopathy were identified by metabonomic analysis, and Shenfu decoction had significant reversal effect on 11 metabolites. Metabolic pathway analysis showed that the synthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism, phenylalanine metabolism, tricarboxylic acid cycle and dicarboxylic acid metabolism were the main targeted metabolic pathways of Shenfu decoction. Conclusion Shenfu decoction can reverse adriamycin-induced cardiomyopathy by regulating the unbalanced synthesis of phenylalanine, tyrosine and tryptophan, as well as the metabolism of arachidonic acid, phenylalanine, dicarboxylic acid and tricarboxylic acid cycle.

4.
Article in Chinese | WPRIM | ID: wpr-906084

ABSTRACT

Objective:To study the protective effect of the Wenyang Huoxue Huatan prescription (WYHXHT) on cardiotoxicity induced by adriamycin. Method:SD rats were randomly divided into the following six groups: a normal control group, an adriamycin model group, a low-dose (4.86 g·kg<sup>-1</sup>) WYHXHT group, a middle-dose (9.72 g·kg<sup>-1</sup>) WYHXHT group, a high-dose (19.44 g·kg<sup>-1</sup>) WYHXHT group, and a dexrazoxane group. Except for the normal control group, the rats in other groups received intraperitoneal injection of 2.5 mg·kg<sup>-1</sup> adriamycin, once a week for six weeks, with a cumulative dose of 15 mg·kg<sup>-1</sup>. The normal control group, the adriamycin model group, and the dexrazoxane group received 10 mL·kg<sup>-1</sup> normal saline daily by gavage. In the dexrazoxane group, the rats were subjected to intraperitoneal injection of 25 mg·kg<sup>-1</sup> dexrazoxane 30 min before doxorubicin administration, once a week for six weeks. The general condition of rats was observed and their body weight was monitored. A high-resolution micro-ultrasound imaging system was used to detect rat cardiac function. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes of myocardial tissues of rats. Western blot was used to detect the protein expression of microtubule-associated protein 1 light chain 3 (LC3) Ⅱ, the mammalian homolog of yeast Atg6 (Beclin-1), and p62 protein in rat myocardial tissues. Result:Compared with the normal control group, rats in the adriamycin model group showed dull fur, reduced food intake and activity, loose stool, low energy, and slow response. Besides, it also displayed reduced body weight (<italic>P</italic><0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (<italic>P</italic><0.01), myocardial cell degeneration, edema, rupture, and dissolution, expansion of myocardial interstitium, uneven staining of myocardial fiber, visible inflammatory cell infiltration, up-regulated expression of Beclin-1 and LC3Ⅱ in rat myocardial tissues (<italic>P</italic><0.01), and down-regulated p62 expression (<italic>P</italic><0.01). Compared with the adriamycin model group, the medium- and high-dose WYHXHT groups exhibited increased body weight, LVEF, and LVFS (<italic>P</italic><0.01), relieved pathological injury of myocardial tissues, down-regulated expression of LC3Ⅱ and Beclin-1 (<italic>P</italic><0.05,<italic>P</italic><0.01), and up-regulated expression of p62 (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:WYHXHT can effectively prevent and treat adriamycin-induced cardiotoxicity, and its effect may be related to the inhibition of myocardial cell autophagy. The effect is dominant in the high-dose group.

5.
Chinese Journal of Biotechnology ; (12): 2522-2533, 2021.
Article in Chinese | WPRIM | ID: wpr-887818

ABSTRACT

To explore the immunomodulatory effect of adriamycin on 4T1 breast cancer. We used a tandem mass tag-based quantitative proteomic method to detect differential proteins in breast cancer tissues, and multiple bioinformatics databases to analyze the differentially expressed proteins in the proteome. Also, we used enzyme-linked immunosorbent assay to detect the effects of adriamycin on helper T cells 1 and 2 in breast cancer tissues, and flow cytometry to detect CD4+ T cells, CD8+ T cells and regulatory T cells. We discovered the immunomodulatory targets of adriamycin in differential proteins. In total 170 differential proteins were significantly up-regulated, whereas 58 were markedly down-regulated. In addition, 73 proteins were involved in immune regulation. Kyoto encyclopedia of genes and genomes enriched important protein pathways related to cytokines and factor receptors, interleukin 17 pathway and cancer transcriptional regulatory pathways. These pathways and important differential proteins related to immunomodulatory functions were ultimately regulated by adriamycin on CD4+ T cells, CD8+ T cells and regulatory T cells, thereby affecting the prognosis of breast cancer. Moreover, adriamycin significantly increased interleukin 2, CD4+ T and CD8+ T (P<0.01) and markedly reduced regulatory T cells (P<0.05). The function of adriamycin against triple-negative breast cancer was closely related to the immunoregulation process of the differential proteins Ighm, Igkc, S100A8, S100A9 and Tmsb4x. Adriamycin could regulate the content of helper T cells 1 cytokines, CD4+ T and CD8+ T lymphocytes in breast cancer and reduce the number of regulatory T cells to produce immunomodulatory effects.


Subject(s)
Animals , Breast Neoplasms/drug therapy , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Disease Models, Animal , Doxorubicin/pharmacology , Female , Humans , Mice , Proteomics
6.
Article in Chinese | WPRIM | ID: wpr-883371

ABSTRACT

Objective: To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats. Methods: The rats were divided into 4 groups. The control group received solvent; the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days; the adriamycin group was administered with a single dose of adriamycin (15 mg/kg, i.p.), and the p-coumaric acid + adriamycin group was given p-coumaric acid five days before adriamycin administration. Twenty-four hours after the last administration, blood samples were collected for biochemical analysis, and liver tissues were removed for histopathological and immunohistochemistrical studies. Moreover, the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in liver tissue were measured. Results: Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase, alanine transaminase, aspartate transaminase, total bilirubin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin. p-Coumaric acid also raised the levels of glutathione peroxidase, superoxide dismutase, and catalase, as well as decreased lipid peroxidation in liver tissue and hepatic IL-1β expression. Additionally, histopathological study confirmed the protective effect of p-coumaric acid against liver damage. Conclusions: p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.

7.
J Ayurveda Integr Med ; 2020 Apr; 11(2): 118-123
Article | IMSEAR | ID: sea-214126

ABSTRACT

Background: Rasashastra needs to be upgraded using the technological advances, with regards to drugprocessing, development and therapeutics. The potential of Rasaaushadhis need to be explored by subjecting them against newer life threatening diseases like cancer where contemporary medicine haslimitations. Abhrak Bhasma, one of the drugs of Rasashastra, has some peculiar attributes. According toclassical Rasashastra texts, Shataputi Abhrak Bhasma is regarded as a Rasayan, whose efficacy is in directproportion to the number of Putas. Thus increasing number of Putas not only has a significant effect onthe physical, analytical aspects but also the therapeutic effect of the Abhrak Bhasma.Objectives: To screen in vitro anticancer activity of Abhrak Bhasma at various stages of Putas (20, 50, 100).To evaluate and thus validate the principle from classical Rasashastra texts, which explains direct relationof number of Putas with therapeutic efficacy.Materials and methods: Shataputi Abhrak Bhasma, at various stages of its preparation was subjected toin vitro anticancer activity on three different cancer cell lines (LungHOP62, LeukemiaU937, ProstateDU145) at Tata Memorial Centre- Advanced Centre for Treatment, Research Education in Cancer, NaviMumbai. SRB assay was followed to evaluate the anti-proliferative activity.Results: It was found that Abhrak Bhasma shows concentration dependent positive in vitro anticanceractivity on all three cell lines with highly significant activity on prostate cancer cell lines. Anticanceractivity of Abhrak Bhasma is in the order 100 Puti > 50 Puti > 20 Puti. Shataputi Abhrak Bhasma hadmaximum activity on prostate cancer cell lines almost equivalent to positive control drug adriamycin.Conclusion: The in vitro anticancer activity of Shataputi Abhrak Bhasma increases with increasing numberof Putas, thus revalidating the direct relation between number of Putas and efficacy of the drug.© 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V

8.
Article in Chinese | WPRIM | ID: wpr-846668

ABSTRACT

Objective: To observe the reversal and prevention effect of New Shengmai Decoction on the rats’ cardiomyocyte apoptosis induced by adriamycin, and provide the experimental foundation basis for the clinical treatment of myocardial injury induced by adriamycin. Method: The rat models with cardiomyocyte apoptosis were established by adriamycin. Forty male SD rats were divided randomly into four groups, including the normal group, the adriamycin model group, the captopril group and the New Shengmai Decoction group. During the experiment, the mental state, activity, feeding, hair color and other conditions of the rats were observed. After 6 weeks of treatment, the cardiac function and left ventricular hypertrophy of rats were measured and the pathological changes of myocardium were observed by HE staining. And the apoptosis of myocardial cells was observed by TUNEL staining and protein expressions of Caspase-3, Bcl-2, and Bax were detected by immunohistochemistry. Results: Compared with the control group, the cardiac function of the model group was significantly decreased. Compared with the model group, the cardiac function of rats after the different drugs’ treatment could be improved in the different degrees and the effect of the New Shengmai Decoction group was significant. Compared with the control group, the heart body ratio, left ventricular hypertrophy index and myocardial cell apoptosis index in the model group were all significantly increased. Compared with the model group, the captopril group and the New Shengmai Decoction group ameliorated cardiac hypertrophy and myocardial cell apoptosis in rats. Compared with the control group, the expression level of bcl-2 protein in the model group was decreased, while the expression level of Bax and Caspase-3 protein was increased. Compared with the model group, captopril and the New Shengmai Decoction increased the expression level of bcl-2 protein and decreased the expression level of Bax and Caspase-3 protein. Conclusion: The New Shengmai Decoction can improve the cardiac function and lessen cardiomyocyte apoptosis of rats. It can also decrease the expression of protein Caspase-3 in the cardiac muscle of rats or inhibit its activity. In order to restrain cardiomyocyte apoptosis, the New Shengmai Decoction can increase the expression of protein Bcl-2 and decrease the expression of protein Bax through improving the expression of Bcl-2/Bax in the cardiac muscle of rats.

9.
Ginecol. obstet. Méx ; 87(4): 268-275, ene. 2019. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1250032

ABSTRACT

Resumen ANTECEDENTES: La relación entre cáncer y embarazo supone 0.07% de las complicaciones gestacionales. Cuando estas situaciones coinciden el tratamiento del tumor se dificulta. El tumor neuroectodérmico primitivo es una neoplasia relacionada con el sarcoma de Ewing y su incidencia es excepcional durante el embarazo. CASO CLÍNICO: Paciente de 34 años, con 36.3 semanas de embarazo, que ingresó a la unidad hospitalaria por dolor abdominal irradiado al miembro inferior derecho. A la exploración física se palpó una tumoración de gran dimensión en la fosa iliaca derecha. La ecografía abdominal objetivó una imagen compatible con un mioma. La resonancia magnética reportó una masa de 16 x 13 x 17 cm, retroperitoneal, paravertebral, coincidente con tumor neuroectodérmico, sarcoma y tumor neurogénico. La paciente tuvo parto eutócico, sin administración de analgesia epidural, del que nació una niña de 2950 g, con Apgar 8-9. Se efectuó una biopsia por aspiración con aguja gruesa, que reportó un tumor neuroectodérmico primitivo. El tratamiento consistió en quimioterapia con protocolo VAC (vincristina, dactinomicina y ciclofosfamida [14 ciclos]) y adriamicina (6 a 8 ciclos de inducción). Actualmente padece dolor neuropático en la pierna derecha y permanece en rehabilitación, con tratamiento médico. CONCLUSIONES: Los tumores neuroectodérmicos primitivos son neoplasias excepcionales durante el embarazo. Se requieren estudios complementarios para conocer la relación exacta entre este tipo de tumores y el embarazo, y de esta forma establecer el protocolo de tratamiento adecuado.


Abstract BACKGROUND: The relationship between cancer and pregnancy accounts for 0.07% of gestational complications. This aspect makes treatment difficult and has a negative impact on pregnant patients. The primitive neuroectodermal tumor is a neoplasm related to Ewing's sarcoma and its incidence is exceptional during pregnancy. CLINICAL CASE: A 34-year-old patient, 36.3 weeks pregnant, who was admitted to the hospital unit due to abdominal pain radiating to the right lower limb. Physical examination revealed a large tumor in the right iliac fossa. The abdominal ultrasound showed an image compatible with a myoma. Magnetic resonance imaging revealed a mass of 16 x 13 x 17 cm, retroperitoneal, paravertebral, coinciding with neuroectodermal tumor, sarcoma and neurogenic tumor. The patient had eutocic delivery, without administration of epidural analgesia, from which a girl of 2950 g was born, and Apgar 8/9. An aspiration biopsy was performed with a thick needle, which reported a primitive neuroectodermal tumor. The treatment consisted of chemotherapy with VAC protocol (vincristine, dactinomycin and cyclophosphamide [14 cycles]) and adriamycin (6 to 8 induction cycles). He currently suffers from neuropathic pain in the right leg and remains in rehabilitation, with medical treatment. CONCLUSIONS: Primitive neuroectodermal tumors are exceptional neoplasms during pregnancy. Complementary studies are required to know the exact relationship between this type of tumors and pregnancy, and in this way establish the appropriate treatment strategy.

10.
Chinese Pharmaceutical Journal ; (24): 987-991, 2019.
Article in Chinese | WPRIM | ID: wpr-857988

ABSTRACT

OBJECTIVE: To investigate the inhibitiom effect of PTEN(gene of phosphate and tension homology deleted on chromsome ten) combined with adriamycin on proliferation, migration and invasion of non-Hodgkin lymphoma cell line Raji in vitro. METHODS: Cell proliferation was determined by MTT in Raji cells response to adriamycin with different concentrations. Transwell assay was performed to evaluate the effects of adriamycin and PTEN on migration and invasion of Raji cells. RT-qPCR was conducted to measure the expression of PTEN in Raji cells after adriamycin treatment. RESULTS: Adriamycin significantly inhibited the proliferation of Raji cells in a concentration dependent manner (r=-0.925, P<0.001). Adriamycin inhibited invasion and migration in Raji cells. Moreover, adriamycin promoted the expression of PTEN. Overexpression of PTEN markedly suppressed invasion and migration in Raji cells. The combination of adriamycin and PTEN strikingly decreased the proliferation, invasion and migration of Raji cells. CONCLUSION: Adriamycin and PTEN would inhibite the proliferation, invasion and migration of Raji cells. PTEN drastically enhances the inhibition of adriamycin on the proliferation, migration and invasion of Raji cells.

11.
Article in Chinese | WPRIM | ID: wpr-802232

ABSTRACT

Objective: To investigate the protective effect of Perillae Folium with aqueous extract (PFAE) on some key factors of Adriamycin (ADR)-induced oxidative injury in human renal tubular epithelial cells(HK-2), including the survival rate, oxidative injury indexes and cell apoptosis,in order to define the underlying mechanism. Method: A model of ADR-induced HK-2 cells oxidative injury was established in vitro, then cell viability was detected by cell counting kit-8 (CCK-8) after intervention with positive reference N-acetylcysteine (NAC) or PFAE (5,15,45 g·L-1) at different concentrations. According to the morphological changes under microscopy, the optimum concentration of PFAE was screened out for the follow-up experiments. Then, the experiments were divided into six groups:blank group, ADR (0.05 g·L-1) group, PFAE (15 g·L-1) group, ADR+PFAE (0.05+15) g·L-1 group, NAC (0.81 g·L-1) group, and ADR+NAC (0.05+81) g·L-1 group. After that, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity(TAC) were measured in the cell homogenate after 24 h administration. The level of reactive oxygen species (ROS) was detected by 2',7'-dichloroflurescin diacetate (DCFH-DA) fluorescence probe. Flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to monitor the cell apoptosis. Western blot was used to observed the expressions of mitochondrial apoptosis-associated proteins, like B lymphocyte tumor-2 gene (Bcl-2), Bcl-2 related X protein (Bax), cysteine aspartate protease-9 (Caspase-9), cysteine aspartate protease-3 (Caspase-3) and poly ADP-ribose polymerase (PARP), as well as their shear bodies. In addition, the phosphorylation protein expressions of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signaling transduction pathway were detected by Western blot. Result: Compared with blank group, ADR group showed a decreased cell viability (PPPPPPPP-1. The ATC and SOD levels were increased in ADR+PFAE group and ADR+NAC group (PPConclusion: PFAE could alleviate the oxidative injury of HK-2 cells induced by ADR, and have an antioxidant effect, which inhibited cell apoptosis through mitochondrial apoptotic pathway and ERK/p38 MAPK signaling pathway.

12.
Article in Chinese | WPRIM | ID: wpr-802094

ABSTRACT

Objective: To observe the preventive and therapeutic effect of Huanglian Ejiao Tang on myocardial injury induced by anthracycline chemotherapeutic drugs in all kinds of cancer patients undergoing chemotherapy. Method:We chosen all kinds of cancer patients with combined use of anthracycline chemotherapy drugs in our hospital, 21 days as one cycle. The cardiac toxicity reaction was observed after three continuous chemotherapy cycles. A total of 64 patients who met the dialectical criteria of "imbalance between heart-Yang and kidney-Yin" were randomly divided into treatment group (32 cases) and control group (32 cases). Patients in treatment group were treated with Chinese medicine Huanglian Ejiao Tang based on original chemotherapy regimen, adding and subtracting Chinese medical materials according to the symptoms. Patients in control group continued to maintain the original chemotherapy regimen, and both two groups of patients continued to receive 3 cycles of continuous chemotherapy. By comparing the cardiac function classification and cardiac function tolerance between the 3 cycles and 6 cycles of two groups of patients after chemotherapy; changes of echocardiography index, QTc interval, creatine kinase isoenzyme (CK-MB), Myoglobin (MYO), cardiac troponin I (cTNI)and nitrogenous terminal-pro-brain natriuretic peptide(NT-pro-BNP) concentration value were compared between two groups; and the concentrations of adrenaline (E), norepinephrine (NE) and angiotensin Ⅱ(AngⅡ) were observed and compared; meanwhile, the correlation analysis was carried out at the same time. Result:After 6 cycles of chemotherapy in Chinese medicine treatment group, degree of cardiac function classification and the 6 minute walking heart function tolerance were significantly better than those at the 3 cycles of chemotherapy (PPPPPConclusion:Huanglian Ejiao Tang can reduce the excitability of the symppthetic nervous system (SNS) and renin-angiotensin system(RAS) in human body and inhibit the release level of NE, E and AngⅡ by effect of "invigorating the kidney and clearing the heart". It has a certain preventive and treatment effect on the cardiac toxicity of patients with the cumulative use of anthracycline chemotherapy. To a certain extent, it can inhibit myocardial injury, improve cardiac function and reduce the incidence of cardiovascular events.

13.
Article in Chinese | WPRIM | ID: wpr-801693

ABSTRACT

Renal fibrosis is a common pathological change in the later stages of all kidney diseases. It is a multi-cytokine, multi-signal pathway, multi-factor driven chronic kidney disease. It includes renal interstitial fibrosis, tubular sclerosis and glomerular sclerosis, which eventually leads to chronic renal failure. From health through injury to loss of function, the disease process is closely related to the degree of deterioration of renal function and the prognosis of chronic kidney disease. There is no effective western medicine for the treatment of renal fibrosis. Professor HE Liqun from Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine has summarized the Kangxianling decoction through decades of long-term practical experience. It has the effects in strengthening the spleen and replenishing Qi, clearing away dampness and heat, promoting blood circulation and removing phlegm, and strengthening turbidity. It is composed of Salviae Miltiorrhizae Radix et Rhizoma 15 g, Persicae Semen 12 g, Angelicae Sinensis Radix 12 g, Achyranthis Bidentatae Radix 9 g, Rhei Radix et Rhizoma 15 g. Kangxianling can affect the synthesis and secretion of cytokines and inflammatory factors by expanding blood vessels, and can improve renal tubular fibrosis. It has a good multi-channel, multi-target and multi-directional protective effect on renal function. It also can delay the progress of chronic renal fibrosis by significantly alleviating such symptoms as fatigue and edema in patients with chronic renal fibrosis, and reducing serum creatinine, urea nitrogen and urine protein. In this paper, 5/6 nephrectomy, ischemia reperfusion injury, adriamycin-induced nephropathy, unilateral ureteral obstruction and other different modeling methods are listed. The mechanism of Kangxianling decoction in antagonizing renal fibrosis is discussed and summarized, which further provided new ideas and directions for future clinical and scientific research.

14.
Article in Chinese | WPRIM | ID: wpr-851413

ABSTRACT

Objective To study the efficacy enhancing and toxicity reducing effects of compatibility of Aconitum carmichaeli and Cornus officinalis on chronic heart failure (CHF) rats. Methods The CHF rats was established by ip injection of adriamycin (ADM), the CHF rats were administrated tested drugs for three weeks by means of ig administration, the tested drugs included extracts of A. carmichaeli, C. officinalis, and Compound. The serum brain natriuretic peptide (BNP) level, activity of Ca2+-ATP and Na+, K+-ATP enzymes in cardiac myocytes, and cardiac histopathology were measured. Results After three weeks of modeling, the CHF rats showed signs of ascites, loss of weight, loose stool, hogback, etc. The left ventricular ejection fraction (EF) and fraction shortening (FS) decreased significantly, and the level of BNP in serum was significantly improved; Pathological changes of ventricular tissue included rupture of myocardial fibers, degeneration and necrosis of cardiomyocytes, etc. After three weeks of gavage compatibility of A. carmichaeli and C. officinalis, the general state and cardiac histopathology of the animal was obviously improved, the level of BNP in serum was reduced significantly, the activity of Na+, K+-ATP enzymes was increased significantly. No notable improvement in the above indexes was obtained after administration of A. carmichaeli and C. officinalis alone. Conclusion The compatibility of A. carmichaeli and C. officinalis can increase the activity of Na+, K+-ATP enzyme in cardiac myocytes, and improve the energy metabolism and activity of cardiac myocytes in chronic heart failure. The compatibility of A. carmichaeli and C. officinalis play the key role of enhancing efficacy and reducing toxicity.

15.
Article in Chinese | WPRIM | ID: wpr-841642

ABSTRACT

Objective: To construct the recombinant lentiviral vector containing cardiac adriamycin responsive protein (CARP) gene and small-hairpin RNA (shRNA) targeting CARP gene and to pack the lentivirus, and to lay the foundation for further study on the function and mechanism of CARP in adriamycin (ADR) induced cardiomyopathy. Methods: After the rat CARP gene was amplified by PCR and shRNAs targeting CARP were designed and synthesized, they were inserted into the shuttle plasmids GV-358 or GV-248. respectively. After confirmed by sequencing, the recombinant shuttle vectors containing CARP gene or shRNA and auxiliary packaging plasmid Helper 1 0 and Helper 2 0 were co transfected into the IIEK293T cells for virus packaging and amplification; the viral titer was detected by end point dilution. The IIEK293T cells were infected with the recombinant lentiviruses. and the green fluoresence intensity was observed by fluorescence mircroscope. The H9C2 cells were infected with the recombinant lentivirues and divided into control group. CARP overexpression group and shRNA group; Western blotting method was used to detect the CARP expression levels in the cells in various groups. Results: The DNA sequencing results showed that the sequences of CARP overexpression and shRNA vectors were in accordance with the designed sequences. The expression of green fluorescence protein was seen under fluorescence microscope after transfection of the vectors of the IIEK293T cells. After infection of the H9C2 cells, the expression level of CARP protein in CARP overexpression group was 5. 3 times higher than that in control group ( P=0. 01); while it was down-regulated by 53% in CARP shRNA group compared with control group ( P= 0 02). Conclusion: The lentivirus expression vectors carrying CARP or shRNA targeting CARP are successfully constructed and the lentiviruses obtained could significantly interfere the expression of CARP in the II9C2 cells.

16.
China Pharmacy ; (12): 2752-2757, 2019.
Article in Chinese | WPRIM | ID: wpr-817515

ABSTRACT

OBJECTIVE: To prepare Adriamycin hydrochloride (DOX) magnetic thermosensitive liposome (MTSL), investigate its physicochemical properties, magnetic effect and photothermal effect, so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS: Using DOX as model drug, TiO2@Fe3O4 as photosensitizers and magnetic materials, DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed; particle size and Zeta potential were detected; encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution, in vitro release behavior of the liposome was investigated by dialysis method, and the release curves at different temperatures (at 37, 43 ℃) were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species (ROS) in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS: Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion, and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm; polydispersity index was 0.107; Zeta potential was (-7.76±3.41)mV; encapsulation efficiency was (92.3±3.2)%. Under the external magnetic field, the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution, the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃, the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser (808 nm) irradiation time, the temperature of the liposome kept rising, which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS: DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully, which has uniform appearance, good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency, and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.

17.
China Pharmacy ; (12): 15-20, 2019.
Article in Chinese | WPRIM | ID: wpr-816741

ABSTRACT

OBJECTIVE: To investigate the effects of ligustrazine structural modification product Liguzinediol on hemodynamics in chronic heart failure (CHF) model rats induced by adriamycin. METHODS: SD rats were given intraperitoneal injection of adriamycin (2 mg/kg) to induce CHF model. Model rats were randomly divided into normal saline group, positive control group (Deacetyl tricyanidin injection, 0.022 5 mg/kg) and Liguzinediol low-dose, medium-dose and high-dose groups (5, 10, 20        mg/kg), with 8 rats in each group. Other 8 normal rats were selected as blank control group (normal saline). Each group was given relevant medicine intravenously. The left ventricular systolic pressure (LVSP), maximal rate of rise or drop of left ventricular     (±dp/dtmax), systolic pressure (SP), diastolic pressure (DP), heart rate (HR) and other hemodynamic indexes were recorded by multichannel physiological recorder at 1, 5, 10, 20, 40, 60, 90, 120 min after medication. RESULTS: Compared with blank control group, LVSP, +dp/dtmax, │-dp/dtmax│, SP, HR and DP at 120 min after medication of normal saline group were decreased significantly (P<0.05). Compared with normal saline group, LVSP at 5-60 min after medication, +dp/dtmax at 40-90 min after medication, SP at 10-40 min after medication were increased significantly in Liguzinediol low-dose group (P<0.05 or P<0.01). LVSP at 5-90 min after medication, SP at 10-60 min after medication, DP at 10-60 min (except for 20 min) after medication were increased significantly in Liguzinediol medium-dose group (P<0.05 or P<0.01). LVSP at 1-120 min after medication, +dp/dtmax at 5-90 min after medication, │-dp/dtmax│, and SP at 5-60 min after medication, DP at 40-60 min after medication were increased significantly in Liguzinediol high-dose group (P<0.05 or P<0.01). CONCLUSIONS: Single intravenous injection of Liguzinediol can significantly enhance ventricular systolic function of CHF model rats so as to control or relieve CHF.

18.
Acta Pharmaceutica Sinica B ; (6): 782-793, 2019.
Article in English | WPRIM | ID: wpr-774943

ABSTRACT

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague-Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

19.
Article in Chinese | WPRIM | ID: wpr-773524

ABSTRACT

OBJECTIVE@#To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on hematopoietic function in rats after combined chemotherapy with doxorubicin and cyclophosphamide.@*METHODS@#Eighty rats were randomized into control group and LIPUS group (=40) for treatment with intraperitoneal injection of doxorubicin (2 mg/kg)+cyclophosphamide (20 mg/kg) for 4 consecutive days and continuous irradiation with LIPUS for 7 days following the injections, respectively. The white blood cells, red blood cells and platelets counts in each group were measured at 0, 4, 7, 9, 11, 14 and 18 days after the start of drug administration. The pathological sections of the bone marrow were examined at 0, 4 and 11 days, and the flow cytometry was performed for detecting the cell apoptosis; qPCR was performed for detecting the expressions of SCF, ICAM-1, and VCAM-1 mRNAs, and ELISA was used to detect the expressions of IL-3 and GM-CSF.@*RESULTS@#The white blood cell count was significantly higher in LIPUS group than in the control group ( < 0.05). Histopathological examination of the bone marrow revealed significantly increased hematopoietic tissue in LIPUS group ( < 0.05). Flow cytometry demonstrated an obviously lower cell apoptosis rate in the bone marrow in LIPUS group than in the control group ( < 0.05). Compared with those in the control group, the mRNA expression levels of ICAM-1 and VCAM-1 as well as the protein levels of IL-3 and GM-CSF were significantly increased in LIPUS group ( < 0.05).@*CONCLUSIONS@#LIPUS can alleviate the hematopoietic damage after combined chemotherapy with doxorubicin with cyclophosphamide probably by increasing the expressions of ICAM- 1, VCAM-1, IL- 3, and GM-CSF.


Subject(s)
Animals , Bone Marrow , Cyclophosphamide , Doxorubicin , Hematopoietic Stem Cell Transplantation , Rats , Ultrasonic Waves
20.
Int. j. morphol ; 36(1): 48-53, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-893185

ABSTRACT

SUMMARY: Doxorubicin is a drug that used by a majority in the treatment of carcinomas. The most obvious known side effect is cardiomyopathy. Many studies have been carried out to eliminate side effects of the doxorubicin, and stem cell studies have been added in recent years. In this study, it was aimed to investigate fetal-derived mesenchymal stem cells (F-MSCs) treatment of doxorubicininduced cardiomyopathy by morphological methods. A total of 24 rats which were divided into three separate groups (Control, sham, treatment), each consisting of 8 male rats were used. In sham and treatment group, Adriamycin was administered in a single dose by tail injection to perform cardiotoxicity. In the treatment group, F-MSCs were intra-peritoneally administrated. Then, rats were euthanized and their hearts were photographed at the level of papillary muscle. and thickness, diameters and surface area levels were measured. Left ventricular mass (LVM) and left ventricular mass index (LVMI) were calculated after measurement. The sham group, LVM and LVMI levels were found to significantly lower (p<0.05) than control and treatment group. In the one hand, LVMI levels of rats in treatment group was statistically similar (p>0.05) to control group. Similarly, LVM levels of control and treatment groups were close to each other while this level of sham group was lower. It has been shown that F-MSC administrations in rats with doxorubicin-induced cardiomyopathy have adverse effect on LVM and LVMI values. In addition, the intra-peritoneal MSC administrations may be an alternative to other injection routes such as intra-venous and intra-cardiac administrations.


RESUMEN: La doxorrubicina es un medicamento usado ampliamente en el tratamiento de carcinomas. El efecto secundario más conocido es la miocardiopatía. Se han llevado a cabo muchos estudios para eliminar los efectos secundarios de la doxorrubicina, y en los últimos años se han agregado estudios con células madre. mediante métodos morfológicos, se intentó investigar el tratamiento de las células madre mesenquimales (F-MSCs) derivadas del feto, de la miocardiopatía inducida por doxorrubicina. Se utilizó un total de 24 ratas que se dividieron en tres grupos (control, simulación, tratamiento), cada uno de las cuales consistía en 8 ratas macho. En el tratamiento simulado y en el grupo tratamiento, se administró doxorrubicina en una dosis única mediante inyección en la cola de la rata para realizar cardiotoxicidad. En el grupo tratamiento, las FMSC se administraron intraperitonealmente. Luego, las ratas fueron sacrificadas y sus corazones fueron fotografiados a nivel de los músculos papilares, y se midieron los espesores, los diámetros y los niveles de área superficial. Después de las mediciones se calcularon la masa ventricular izquierda (MVI) y el índice de masa ventricular izquierda (IMVI). En el grupo simulado, los niveles de MVI y IMVI se encontraron significativamente inferiores (p <0.05) que en los grupos control y tratamiento. Por un lado, los niveles de IMVI de las ratas en el grupo de tratamiento fueron estadísticamente similares (p> 0,05) al grupo de control. De forma similar, los niveles de MVI de los grupos control y tratamiento se aproximaban uno al otro, mientras que este nivel era más bajo en el grupo simulado. Se ha demostrado que la administracion de F-MSC en ratas con miocardiopatía inducida por doxorrubicina tiene un efecto adverso sobre los valores de MVI y IMVI. Además, la administracion de MSC intraperitoneal puede ser una alternativa a otras rutas de inyección tal como las administración intravenosa e intracardíaca.


Subject(s)
Animals , Male , Rats , Cardiomyopathies/drug therapy , Heart Ventricles/drug effects , Pluripotent Stem Cells , Cardiomyopathies/chemically induced , Doxorubicin/toxicity , Heart Ventricles/pathology , Rats, Sprague-Dawley
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