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المؤلفون: Walaa F. Alsanie, Majid Alhomrani, Syed Mohammed Basheeruddin Asdaq, Abdulrahman Hadi Almutiri, Abdulhakeem S. Alamri, Obulesu Challa, Majed Sadun Alshammari
المصدر: Molecules
Molecules, Vol 26, Iss 3203, p 3203 (2021)
Volume 26
Issue 11مصطلحات موضوعية: myocardial disturbance, 030309 nutrition & dietetics, Thiobarbituric acid, Pharmaceutical Science, Organic chemistry, 030204 cardiovascular system & hematology, Antioxidants, Analytical Chemistry, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, QD241-441, Drug Discovery, Creatine Kinase, MB Form, Carvedilol, 0303 health sciences, biology, Heart, Catalase, S-allyl cysteine, metabolic derangements, Chemistry (miscellaneous), Molecular Medicine, Female, medicine.drug, medicine.medical_specialty, S-Allyl cysteine, carvedilol, Thiobarbituric Acid Reactive Substances, Article, Superoxide dismutase, 03 medical and health sciences, Necrosis, cytoprotection, Lactate dehydrogenase, Internal medicine, aged garlic extract, medicine, TBARS, Animals, Cysteine, Physical and Theoretical Chemistry, Garlic, L-Lactate Dehydrogenase, isoproterenol, Plant Extracts, Superoxide Dismutase, Myocardium, Hemodynamics, Rats, Endocrinology, chemistry, biology.protein, Creatine kinase
الوصف: This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::190076fd790f0d41b781531333ed5952Test
http://europepmc.org/articles/PMC8198312Test -
102
المؤلفون: Zahra Bagheri-Hosseinabadi, Shahrzad Zadehmodarres, Mohammad Asnaashari, Nabaa Najjar, Fatemeh Javani Jouni, Jaber Zafari
المصدر: J Lasers Med Sci
مصطلحات موضوعية: Urology, medicine.medical_treatment, Photodynamic therapy, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, medicine, Dentistry (miscellaneous), Orthopedics and Sports Medicine, Cisplatin, Cervical cancer, Chemotherapy, business.industry, Cancer, 030206 dentistry, medicine.disease, chemistry, Nephrology, Apoptosis, Cancer cell, Cancer research, Original Article, Surgery, business, medicine.drug
الوصف: Introduction: Cervical cancer is recognized as one of the major causes of mortality among elderly women. Although there are several different therapeutic worldwide guidelines, many researchers have focused on screening new methodologies and technologies to elevate the efficiency of cervical cancer treatment. The simultaneous use of photodynamic therapy (PDT) along with chemotherapy as cisplatin has achieved good aims in the treatment of cervical cancer. Methods: A2780 cells were treated with cisplatin, photodynamic progress (laser with methylene blue as a photosensitizer compound) and a combination of cisplatin and PDT. The lithic effect of the laser, methylene blue and their combination and the IC50 value of cisplatin were calculated for each group. The amount of malondialdehyde (MDA) as membrane lipid peroxidation product and released lactate dehydrogenase was measured in the medium. The toxicity of each agent was evaluated by the MTT technique. Results: The results show that a combination of PDT and chemotherapeutic agent cisplatin caused a twofold decrease in viable cervical cancer cells compared to each therapeutic progress. The combination of both laser therapy and cisplatin enhanced cancer cell membrane disruption by increased membrane lipid peroxidation and apoptotic enzyme activation by the elevation of lactate dehydrogenase activity. Conclusion: The results indicated that cisplatin combined with PDT had a greater therapeutic effect on A2780 as a cervical cancer cell line. Therefore, PDT in combination with chemotherapy enhances the effectiveness of chemotherapeutic agents by the disruption of the cancer cell membrane and switching the apoptosis progress with less adverse effects.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67fe2f29f7ffd22c0e7d2abdfd029293Test
https://doi.org/10.34172/jlms.2020.s14Test -
103
المؤلفون: Ling Sang, Liang Kang, Yun Zhang, Xingxiang Wang, Bin Song, Ming Zhong, Li Jiang, Xia Zheng, Zhaohui Qu, Dingyu Zhang, Jiaran Shi, Wang Zhang
المصدر: Aging (Albany NY)
مصطلحات موضوعية: Male, China, cardiac injury, Aging, medicine.medical_specialty, medicine.drug_class, Fibrinogen, Gastroenterology, law.invention, coronavirus disease 2019, chemistry.chemical_compound, law, death, Lactate dehydrogenase, Internal medicine, medicine, Humans, Coagulation Disorder, Aged, Retrospective Studies, biology, SARS-CoV-2, business.industry, Anticoagulant, Anticoagulants, COVID-19, Retrospective cohort study, Cell Biology, Blood Coagulation Disorders, Middle Aged, Troponin, Intensive care unit, Intensive Care Units, Coagulation, chemistry, inflammation, biology.protein, Female, coagulation dysfunction, business, Research Paper, medicine.drug
الوصف: Coagulation dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19) has not been well described, and the efficacy of anticoagulant therapy is unclear. In this study, we retrospectively reviewed 75 fatal COVID-19 cases who were admitted to the intensive care unit at Jinyintan Hospital (Wuhan, China). The median age of the cases was 67 (62–74) years, and 47 (62.7%) were male. Fifty patients (66.7%) were diagnosed with disseminated intra-vascular coagulation. Approximately 90% of patients had elevated D-dimer and fibrinogen degradation products, which decreased continuously after anticoagulant treatment and was accompanied by elevated albumin (all P
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a430d48fdb4e068d02de3957161efa5aTest
https://doi.org/10.18632/aging.202223Test -
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المؤلفون: Peter G. Brindley, Demetrios J. Kutsogiannis, Dimitrios Karakitsos, Abdulrahman Alharthy, Mohammed Alodat, Fahad Faqihi
المصدر: Journal of Critical Care
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, ARDS, Resuscitation, Critical Care, Critical Illness, Multiple Organ Failure, medicine.medical_treatment, Pilot Projects, Critical Care and Intensive Care Medicine, Patient Positioning, Interquartile range, Internal medicine, Prone Position, Humans, Medicine, Prospective Studies, Aged, Mechanical ventilation, Respiratory Distress Syndrome, L-Lactate Dehydrogenase, Plasma Exchange, Interleukin-6, business.industry, Septic shock, COVID-19, Bilirubin, Hydroxychloroquine, Middle Aged, medicine.disease, Respiration, Artificial, Intensive Care Units, Prone position, Cytokine release syndrome, C-Reactive Protein, Treatment Outcome, Ferritins, Female, business, medicine.drug
الوصف: We investigated the effect of therapeutic plasma exchange (TPE) on life-threatening COVID-19; presenting as acute respiratory distress syndrome (ARDS) plus multi-system organ failure and cytokine release syndrome (CRS).We prospectively enrolled ten consecutive adult intensive care unit (ICU) subjects [7 males; median age: 51 interquartile range (IQR): 45.1-55.9 years old] with life-threatening COVID-19 infection. All had ARDS [PaO2/FiO2 ratio: 110 (IQR): 95.5-135.5], septic shock, CRS and deteriorated within 24 h of ICU admission despite fluid resuscitation, antibiotics, hydroxychloroquine, ARDS-net and prone position mechanical ventilation. All received 5-7 TPE sessions (dosed as 1.0 to 1.5 plasma volumes).All of the following significantly normalized (p 0.05) following the TPE completion, when compared to baseline: Sequential Organ Function Assessment score, PaO2/FiO2 ratio, levels of lymphocytes, total bilirubin, lactate dehydrogenase, ferritin, C-reactive protein and interleukin-6. No adverse effects from TPE were observed. Acute kidney injury and pulmonary embolism were observed in 10% and 20% of patients, respectively. The duration of mechanical ventilation was 9 (IQR: 7 to 12) days, the ICU length of stay was 15 (IQR: 13.2 to 19.6) days and the mortality on day-28 was 10%.TPE demonstrates a potential survival benefit and low risk in life-threatening COVID-19, albeit in a small pilot study.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a61587fd4c888944a5d1983702c7d053Test
https://doi.org/10.1016/j.jcrc.2020.07.001Test -
105
المؤلفون: Yajun Duan, Peng Zeng, Xiaoxiao Yang, Dan Zhao, Yuanli Chen, Jihong Han, Shuang Zhang, Chao Xue, Ke Feng, Xiaoju Li, Jiaqi Li
المصدر: Biochemical and Biophysical Research Communications. 533:304-312
مصطلحات موضوعية: Male, 0301 basic medicine, Apoptosis, Pharmacology, medicine.disease_cause, Biochemistry, Mice, chemistry.chemical_compound, Sirtuin 2, 0302 clinical medicine, Myocytes, Cardiac, bcl-2-Associated X Protein, chemistry.chemical_classification, Antibiotics, Antineoplastic, biology, Caspase 3, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Sirtuin, Adiponectin, Oligopeptides, Signal Transduction, medicine.drug, Cardiotonic Agents, Anthracycline, NF-E2-Related Factor 2, Biophysics, Cell Line, Superoxide dismutase, 03 medical and health sciences, Lactate dehydrogenase, medicine, Animals, Doxorubicin, Molecular Biology, Heart Failure, Reactive oxygen species, Cardiotoxicity, Superoxide Dismutase, Myocardium, Cell Biology, Mice, Inbred C57BL, Oxidative Stress, 030104 developmental biology, Gene Expression Regulation, chemistry, biology.protein, Reactive Oxygen Species, Oxidative stress
الوصف: Doxorubicin (DOX) is an anthracycline derivative and widely used as an anticancer drug. However, the severe cardiotoxicity of DOX limits its application. ADP355 is an adiponectin-based active peptide with anti-liver fibrosis and atherosclerosis properties. It remains unclear the effects and involved mechanisms of ADP355 in DOX-induced cardiotoxicity. C57BL/6J mice were intraperitoneally injected DOX once a week to induce heart failure while receiving ADP355 treatment daily for 4 weeks. At the end of experiment, blood and heart tissues were collected. We found that ADP355 markedly improved DOX-induced cardiac dysfunction and histopathological damage, and decreased serum creatine kinase, lactate dehydrogenase and hydroxybutyrate dehydrogenase levels. The anti-apoptotic activity of ADP355 was indicated by reduction in TUNEL-positive cells and cleaved caspase-3 expression, along with decreased BCL2-associated X protein/B cell lymphoma 2 (BAX/BCL2) levels in heart tissues. Additionally, ADP355 markedly increased DOX-decreased cell viability by reducing BAX/BCL2, but inhibited reactive oxygen species production in H9c2 cells. Mechanistically, ADP355 attenuated expression of DOX-reduced nuclear factor-erythroid 2-related factor 2 (Nrf2) and superoxide dismutase 2, as well as mRNA levels of Nrf2 downstream targets. Furthermore, ADP355 activated sirtuin 2 and its target genes. In conclusion, we demonstrate that ADP355 alleviates DOX-induced cardiotoxicity by inhibiting myocardial apoptosis and oxidative stress through Nrf2 and sirtuin 2 signaling pathways. These findings suggest that ADP355 can be a promising candidate for the treatment of cardiac dysfunction.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29c9770580d1054e307c0185994aef56Test
https://doi.org/10.1016/j.bbrc.2020.09.035Test -
106
المؤلفون: Sandra V. Mateo, Damián Escribano, José J. Cerón, Silvia Martínez-Subiela, María Dolores Contreras-Aguilar, Fernando Tecles, Marina López-Arjona, Camila Peres Rubio
المصدر: Research in Veterinary Science. 133:26-30
مصطلحات موضوعية: endocrine system, medicine.medical_specialty, Saliva, Hydrocortisone, Swine, 040301 veterinary sciences, Pain, Transportation, Reproductive physiology, Oxytocin, Esterase, 0403 veterinary science, 03 medical and health sciences, chemistry.chemical_compound, Stress, Physiological, Internal medicine, Lactate dehydrogenase, medicine, Animals, Butyrylcholinesterase, 030304 developmental biology, Swine Diseases, 0303 health sciences, General Veterinary, Chemistry, 04 agricultural and veterinary sciences, Endocrinology, Abattoirs, Biomarkers, hormones, hormone substitutes, and hormone antagonists, medicine.drug
الوصف: Oxytocin is associated with reproductive physiology but also with welfare and positive emotions. In this study, oxytocin was measured in saliva samples of 45 pigs that were collected before being transported to the slaughterhouse, at the time of arrival and 4 h after arrival to the slaughterhouse. Two previously validated assays, one that measures free oxytocin and other that measures oxytocin linked to proteins, were used. In addition, cortisol, salivary alpha-amylase (sAA), total esterase activity (TEA), butyrylcholinesterase (BChE) and lactate dehydrogenase (LDH), which are biomarkers associated with stress and pain in pigs, were measured. The results showed a decrease in free and protein-linked oxytocin concentrations at 4 h after transport compared with the time before transport, while cortisol, sAA, TEA, BChE and LDH showed an increase at 4 h after transport compared with the time before transport. Based on these results it can be concluded that the transport and lairage at slaughterhouse in the conditions of this study produce a decrease in oxytocin in the saliva of pigs that could indicate a reduced emotional well-being.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29174eea6aa0ccabb84763f4c4e5aeddTest
https://doi.org/10.1016/j.rvsc.2020.08.015Test -
107
المؤلفون: Yu Hu, Shaobo Zhou, Mahfoudh A. M. Abdulghani, Hongbin Qiu, Weiqun Wang, Hisham Al-Ward, Salem Baldi, Yu Zhang, Fahmi Shaher, Shu-Qiu Wang
المصدر: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13:4809-4822
مصطلحات موضوعية: Pharmacology, medicine.medical_specialty, business.industry, Cardiomyopathy, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, medicine.disease, medicine.disease_cause, Streptozotocin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, chemistry, Fibrosis, Internal medicine, Lactate dehydrogenase, Diabetic cardiomyopathy, Internal Medicine, medicine, business, Protein kinase B, PI3K/AKT/mTOR pathway, Oxidative stress, medicine.drug
الوصف: Background Ganoderma lucidum spores (GLS) exhibit disease prevention properties, but no study has been carried out on the anti-diabetic cardiomyopathy property of GLS. The aim of this study was to evaluate the hyperglycemia-mediated cardiomyopathy protection and mechanisms of GLS in streptozotocin (STZ)induced diabetic rats. Methods Male SD rats were randomly divided into three groups. Two groups were given STZ (50 mg/kg, i.p.) treatment and when their fasting plasma glucose was above 16.7 mmol/L, among them, one group was given placebo, as diabetic group, and another group was given GLS (300 mg/kg) treatment. The group without STZ treatment was given placebo as a control group. The experiment lasted 70 days. The histology of myocardium and biomarkers of antioxidants, myocardial injury, pro-inflammatory cytokines, pro-apoptotic proteins and phosphorylation of key proteins in PI3K/AKT pathway were assessed. Results Biochemical analysis showed that GLS treatment significantly reduced the blood glucose (-20.3%) and triglyceride (-20.4%) levels compared to diabetic group without treatment. GLS treatment decreased the content of MDA (-25.6%) and activity of lactate dehydrogenase (-18.9%) but increased the activity of GSH-Px (65.4%). Western blot analysis showed that GLS treatment reduced the expression of both alpha-smooth muscle actin and brain natriuretic peptide. Histological analysis on the cardiac tissue micrographs showed that GLS treatment reduced collagen fibrosis and glycogen reactivity in myocardium. Both Western blot and immunohistochemistry analyses showed that GLS treatment decreased the expression levels of pro-inflammatory factors (cytokines IL-1β, and TNF-α) as well as apoptosis regulatory proteins (Bax, caspase-3 and -9), but increased Bcl-2. Moreover, GLS treatment significantly increased the phosphorylation of key proteins involved in PI3K/AKT pathway, eg, p-AKT p-PI3K and mTOR. Conclusion The results indicated that GLS treatment alleviates diabetic cardiomyopathy by reducing hyperglycemia, oxidative stress, inflammation, apoptosis and further attenuating the fibrosis and myocardial dysfunction induced by STZ through stimulation of the PI3K/Akt/mTOR signaling pathway.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::d10495904839b1311a1853f2e8bbdf0cTest
https://doi.org/10.2147/dmso.s281527Test -
108
المؤلفون: Neda Bauman, Olgica Djurković-Djaković, Aleksandra Uzelac, Tijana Štajner, Nataša Terzić-Jovanović, Jelena Srbljanović, Bogdan A. Šolaja, Branko Bobić, Igor Opsenica
المصدر: Journal of Global Antimicrobial Resistance, Vol 23, Iss, Pp 20-25 (2020)
Journal of Global Antimicrobial Resistanceمصطلحات موضوعية: 0301 basic medicine, Microbiology (medical), Plasmodium berghei, 030106 microbiology, Immunology, Malaria, Cerebral, Pharmacology, Microbiology, Aminoquinoline, Antimalarials, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Chloroquine, Lactate dehydrogenase, parasitic diseases, Hyperparasitaemia, Animals, Immunology and Allergy, Medicine, 030212 general & internal medicine, C57BL/6 mice, biology, business.industry, Plasmodium falciparum, biology.organism_classification, medicine.disease, QR1-502, 3. Good health, Malaria, Mice, Inbred C57BL, chemistry, Cerebral Malaria, Aminoquinolines, business, medicine.drug
الوصف: Objectives Malaria treatment is impeded by increasing resistance to conventional antimalarial drugs. Here we explored the activity of ten novel benzothiophene, thiophene and benzene aminoquinolines. Methods In vitro testing was performed by the lactate dehydrogenase assay in chloroquine (CQ)-sensitive Plasmodium falciparum strain 3D7 and CQ-resistant (CQR) P. falciparum strain Dd2. In vivo activity was evaluated by a modified Thompson test using C57BL/6 mice infected with Plasmodium berghei ANKA strain. Results Nine of the ten compounds had a lower 50% inhibitory concentration (IC50) than CQ against the CQR strain Dd2. Five of these compounds that were available for in vivo evaluation were shown to be non-toxic. All five compounds administered at a dose of 160 mg/kg/day for 3 days prolonged the survival of treated compared with untreated mice. Untreated control mice died by Day 7 with a mean parasitaemia of 15%. Among treated mice, a dichotomous outcome was observed, with a two-third majority of treated mice dying by Day 17 with a low mean parasitaemia of 5%, whilst one-third survived longer with a mean hyperparasitaemia of 70%; specifically, five of these mice survived a mean of 25 days, whilst two even survived past Day 31. Conclusions The significant antimalarial potential of this aminoquinoline series is illustrated by its excellent in vitro activity against the CQR P. falciparum strain and significant in vivo activity. Interestingly, compounds ClAQ7, ClAQ9 and ClAQ11 were able to confer resistance to cerebral malaria and afford a switch to hyperparasitaemia to mice prone to the neurological syndrome.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9d25e50e5e45233c8f6574713c9b02cTest
http://www.sciencedirect.com/science/article/pii/S2213716520302022Test -
109
المؤلفون: Piyong Ma, Tianji Liu, Zhijun Li, Jinnan Zhang, Bo Yang, Nan Jiang, Qiong Yu, Yang Liu, Daoyuan Si
المصدر: Open Access Macedonian Journal of Medical Sciences; Vol. 8 No. T1 (2020): T1-Thematic Issue "Coronavirus Disease (COVID-19)"; 436-442
مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Univariate analysis, business.industry, Proportional hazards model, SARS-CoV-2,Risk Factor, RNA, Retrospective cohort study, General Medicine, Disease, Cox Regression, Fibrinogen, Virus, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Internal medicine, Lactate dehydrogenase, medicine, 030212 general & internal medicine, business, Negative Conversion, medicine.drug
الوصف: AIM: To understand the factors associated with negative conversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, targeted surveillance and control measures can be taken to provide scientific basis for the treatment of the disease and to improve the prognosis of the disease. METHODS: Using the method of retrospective cohort study, we collected the data of Coronavirus Disease 2019 (COVID-19) patients in Tongji Hospital of Wuhan, China from 10 January to 25 March, 2020. Among the data of 282 cases, 271 patients, according to whether the negative conversion happened, were divided into negative conversion group and control group. We made the quantitative variables into classification; Chi-square test single-factor and Cox regression were used in univariate analysis and extracted 30 meaningful variables, then through the collinearity diagnosis, excluded the existence of collinear variables. Finally, 22 variables were included in Cox regression analysis. RESULTS: The gender distribution was statistically significant between two groups (p < 0.05). While in the negative conversion group, the patients of non-severe group occupied a large proportion (p < 0.001). The median time for the negative conversion group was 17 days, and at the end of the observation period, the virus duration in control group was 24 days (p < 0.05). A total of 55 variables were included in univariate analysis, among which 30 variables were statistically different between the two groups. After screening variables through collinearity diagnosis, 22 variables were included in the Cox regression analysis. Last, lactate dehydrogenase (LDH), age, fibrinogen (FIB), and disease severity were associated with negative conversion of SARS-CoV-2 RNA. CONCLUSION: Our results suggest that in the treatment of COVID-19, focus on the age of more than 65 years old, severe, high level of LDH, FIB patients, and take some targeted treatment, such as controlling of inflammation, reducing organ damage, so as to provide good conditions for virus clearance in the body.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::472fe1fde06cac5b619f356793d7a8ceTest
https://doi.org/10.3889/oamjms.2020.5488Test -
110
المصدر: Medicinal Chemistry. 16:841-847
مصطلحات موضوعية: Dihydropyridines, Cell Survival, Antiprotozoal Agents, DHPS, Microbial Sensitivity Tests, Microbiology, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Lactate dehydrogenase, parasitic diseases, Drug Discovery, medicine, Humans, Cyst, Cytotoxicity, 030304 developmental biology, Acanthamoeba castellanii, 0303 health sciences, Dose-Response Relationship, Drug, Molecular Structure, biology, 030306 microbiology, Dihydropyridine, biology.organism_classification, medicine.disease, Acanthamoeba, Drug development, chemistry, HeLa Cells, medicine.drug
الوصف: Background: Acanthamoeba is an opportunistic pathogen widely spread in the environment. Acanthamoeba causes excruciating keratitis which can lead to blindness. The lack of effective drugs and its ability to form highly resistant cyst are one of the foremost limitations against successful prognosis. Current treatment involves mixture of drugs at high doses but still recurrence of infection can occur due to ineffectiveness of drugs against the cyst form. Pyridine and its natural and synthetic derivatives are potential chemotherapeutic agents due to their diverse biological activities. Objective: To study the antiamoebic effects of four novel synthetic dihydropyridine (DHP) compounds against Acanthamoeba castellanii belonging to the T4 genotype. Furthermore, to evaluate their activity against amoeba-mediated host cells cytopathogenicity as well as their cytotoxicity against human cells. Methods: Dihydropyridines were synthesized by cyclic dimerization of alkylidene malononitrile derivatives. Four analogues of functionally diverse DHPs were tested against Acanthamoeba castellanii by using amoebicidal, encystation and excystation assays. Moreover, Lactate dehydrogenase assays were carried out to study cytopathogenicity and cytotoxicity against human cells. Results: These compounds showed significant amoebicidal and cysticidal effects at 50 μM concentration, whereas, two of the DHP derivatives also significantly reduced Acanthamoebamediated host cell cytotoxicity. Moreover, these DHPs were found to have low cytotoxicity against human cells suggesting a good safety profile. Conclusion: The results suggest that DHPs have potential against Acanthamoeba especially against the more resistant cyst stage and can be assessed further for drug development.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28e98ce476a178dc1b7634bd88fac1e0Test
https://doi.org/10.2174/1573406415666190722113412Test