RESUMEN
Phenothiazine (PTZ) derivatives have been acknowledged as versatile compounds with significant implications across various areas of medicine, particularly, in cancer research. The cytotoxic effects of synthesized compounds on both normal and cancerous cells, along with their oxidant-antioxidant properties, are pivotal factors in cancer treatment strategies. In the current study, eight new PTZ derivatives were synthesized and the compounds' cytotoxic activities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay while the oxidant-antioxidant properties were evaluated by oxidative stress index (OSI) calculation in SH-SY5Y (a human neuroblastoma cell line), HT-29 (a human colorectal adenocarcinoma cell line), and PCS-201-012 (a human primary dermal fibroblast cell line) cells. Consequently, the half-maximal inhibitory concentration (IC50) values of compound 3a were determined to be 218.72, 202.85, and 227.86 µM while the IC50 values of compound 3b were defined to be 227.42, 199.27, and 250.11 µM in PCS-201-012, HT-29, and SH-SY5Y cells, respectively. Additionally, it was determined that the synthesized compounds demonstrated the lowest OSI in PCS-201-012 cells as compared to the other cell lines.
RESUMEN
The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-ß (TGF-ß), expressions of COX and prostaglandin E2, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.
Asunto(s)
Apoptosis , Ácido Gálico , Indometacina , Inflamación , Estrés Oxidativo , Úlcera Gástrica , Animales , Indometacina/farmacología , Indometacina/toxicidad , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Ratas , Ratas Sprague-Dawley , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Esomeprazol/farmacologíaRESUMEN
Musclin, a myokine, undergoes modulation during exercise and has demonstrated anti-inflammatory effects in cardiomyocytes and glomeruli. However, its role in atherosclerotic responses remains unclear. This study aimed to explore the impact of musclin on inflammatory responses and the interaction between endothelial cells and monocytes under hyperlipidemic conditions. The attachment levels of THP-1 monocytes on cultured HUVECs were examined. Inflammation and the expression of cell adhesion molecules were also evaluated. To explore the molecular mechanisms of musclin, PPARα or heme oxygenase 1 (HO-1) siRNA transfection was performed in HUVECs. The results revealed that treatment with recombinant musclin effectively suppressed the attachment of palmitate-induced HUVECs to THP-1 cells and reduced the expression of cell adhesion proteins (ICAM-1, VCAM-1, and E-selectin) in HUVECs. Furthermore, musclin treatment ameliorated the expression of inflammation markers (phosphorylated NFκB and IκB) in both HUVECs and THP-1 monocytes, as well as the release of TNFα and MCP-1 from HUVECs and THP-1 monocytes. Notably, musclin treatment augmented the expression levels of PPARα and HO-1. However, when PPARα or HO-1 siRNA was employed, the beneficial effects of musclin on inflammation, cell attachment, and adhesion molecule expression were abolished. These findings indicate that musclin exerts anti-inflammatory effects via the PPARα/HO-1 pathway, thereby mitigating the interaction between endothelial cells and monocytes. This study provides evidence supporting the important role of musclin in ameliorating obesity-related arteriosclerosis and highlights its potential as a therapeutic agent for treating arteriosclerosis.
Asunto(s)
Arteriosclerosis , Monocitos , Humanos , Monocitos/metabolismo , PPAR alfa/metabolismo , Células Endoteliales/metabolismo , Hemo-Oxigenasa 1/metabolismo , Inflamación/metabolismo , Moléculas de Adhesión Celular/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Antiinflamatorios/farmacología , Arteriosclerosis/metabolismo , ARN Interferente Pequeño/farmacología , Adhesión Celular , Molécula 1 de Adhesión Celular Vascular/metabolismo , Células Endoteliales de la Vena Umbilical HumanaRESUMEN
PURPOSE: There is very little information about the toxicological and pathological effects of synthetic cannabinoids, which have cannabis-like properties. This study was carried out to histopathologically, hematologically, and biochemically determine the toxic effects of acute and subacute exposure to a novel synthetic cannabinoid 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)indazole-3-carboxamide in internal organs of adult male rats. METHODS: The cannabinoid was injected intraperitoneally at three doses (0.5, 1.0, and 2.0 mg/kg, body weight). The cannabinoid was administered to acute groups for 2 days and to subacute groups for 14 days. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. Hematological and biochemical changes were evaluated and histopathological analyses in lung, liver, and kidney tissues were also performed. RESULTS: No mortality was observed. It was observed that there were fluctuations in hematological and serum biochemical parameters. Among the oxidative stress parameters, significant decreases in superoxide dismutase, catalase levels and significant increases in lipid peroxidation levels were determined. Serious pathological changes such as necrosis, vacuolation, congestion, and fibrosis were observed in the internal organs in a dose-dependent and time-dependent manner. It was also found that the synthetic cannabinoid triggered apoptosis in the organs. The results demonstrated that the most affected organ by the cannabinoid was the kidney. CONCLUSION: This study showed for the first time that CUMYL-4CN-BINACA adversely affects healthy male albino rats. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.
Asunto(s)
Cannabinoides , Riñón , Peroxidación de Lípido , Hígado , Pulmón , Estrés Oxidativo , Animales , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Cannabinoides/toxicidad , Ratas , Hígado/efectos de los fármacos , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Indazoles/toxicidad , Catalasa/metabolismo , Relación Dosis-Respuesta a Droga , Pruebas de Toxicidad Subaguda , Ratas Wistar , Pruebas de Toxicidad AgudaRESUMEN
Methicillinresistant Staphylococcus aureus (MRSA) infections are usually found in hospital settings and, frequently, in patients with open wounds. One of the most critical virulence factors affecting the severity and recurrence of infections is the biofilm; increasing antibiotic resistance due to biofilm formation has led to the search for alternative compounds to antibiotics. The present study aimed to use boric acid and potassium metaborate against MRSA infection in a fibroblast wound model. For this purpose, a twopart experiment was designed: First, MRSA strains were used for the test, and both boric acid and potassium metaborate were prepared in microdilution. In the second step, an MRSA wound model was prepared using a fibroblast culture, and treatments with boric acid and potassium metaborate were applied for 24 h. For the evaluation of the effects of treatment, cell viability assay (MTT assay), analysis of redox stress parameters, including total oxidant status and total antioxidant capacity analyses, lactate dehydrogenase analysis and immunohistochemical staining were performed. In addition, IL1ß and IL10 gene expression levels were assayed. According to the results, potassium metaborate was more effective and exhibited a lower toxicity to fibroblast cells compared to boric acid; moreover, potassium metaborate decreased the level of prooxidant species and increased the antioxidant status more effectively than boric acid. The IL1ß level in the bacteria group was high; however, boric acid and potassium metaborate significantly decreased the expression levels of inflammatory markers, exhibiting the potential to improve the resolution of the lesion. On the whole, the findings of the present study suggest that boric acid and potassium metaborate may be effective on the tested microorganisms.
Asunto(s)
Ácidos Bóricos , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antioxidantes/farmacología , Biopelículas , Ácidos Bóricos/farmacología , Humanos , Oxidación-Reducción , Potasio , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiologíaRESUMEN
BACKGROUND: This study was designed to investigate the neuroprotective effects of bromelain, which is known to have anti-oxidant and anti-inflammatory properties, against the neurotoxicity (induced by 6-OHDA) in SH-SY5Y cells. METHODS AND RESULTS: To establish Parkinson's Disease (PD) model in cell culture conditions, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 1 day. Prior to 6-OHDA treatment, SH-SY5Y cells had been pre-treated with bromelain (25 µg/mL, 50 µg/mL, 75 µg/mL and 100 µg/mL). After 1 day, cell viability was determined with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assays. Oxidative stress was assessed with total antioxidant capacity (TAC), total oxidant status (TOS), glutathione reductase (GR) and malondialdehyde (MDA) analyses. The effect of the bromelain in SH-SY5Ycells was also examined by 4',6-diamidino-2-phenylindole (DAPI) staining. We found that 6-OHDA increased LDH leakage, and cellular apoptosis in SH-SY5Y cells. 6-OHDA aggravated oxidative stress by increasing TOS, MDA and GR and eventually promoted apoptosis in SH-SY5Y cells, while pretreatment with bromelain attenuated these toxic effects of 6-OHDA. CONCLUSIONS: These findings indicated that bromelain, with its neuroprotective features can be useful for neuroprotection in PD.
Asunto(s)
Bromelaínas/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Bromelaínas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Neuronas/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Oxidopamina/efectos adversos , Oxidopamina/farmacología , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
In the title compound, C18H19NO3S, the morpholine ring adopts a chair conformation. The thio-phene ring forms dihedral angles of 26.04â (9) and 74.07â (10)° with the benzene ring and the mean plane of the morpholine ring, respectively. The mol-ecular conformation is stabilized by an O-Hâ¯N hydrogen bond. In the crystal, mol-ecules are connected through C-Hâ¯O hydrogen bonds, forming wave-like layers parallel to the ab plane, which are further linked into a three-dimensional network by C-Hâ¯π inter-actions involving the benzene rings and the methyl-ene H atoms of the morpholine rings.
RESUMEN
In this study, 4-[5-(4-hydroxyphenyl)-3-aryl-4,5-dihydro-1H-pyrazol-1-yl]benzenesulfonamide derivatives (8-14) were synthesized for the first time by microwave irradiation and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS. Cytotoxic activities and inhibitory effects on carbonic anhydrase I and II isoenzymes of the compounds were investigated. The compounds 9 (PSE = 4.2), 12 (PSE = 4.1) and 13 (PSE = 3.9) with the highest potency selectivity expression (PSE) values in cytotoxicity experiments and the compounds 13 (Ki = 3.73 ± 0.91 nM toward hCA I) and 14 (Ki = 3.85 ± 0.57 nM toward hCA II) with the lowest Ki values in CA inhibition studies can be considered as leader compounds for further studies.