RESUMEN
In this study, a novel method for the fabrication of hesperidin/reduced graphene oxide nanocomposite (RGOH) with the assistance of gamma rays is reported. The different RGOHs were obtained by varying hesperidin concentrations (25, 50, 100, and 200 wt.%) in graphene oxide (GO) solution. Hesperidin concentrations (25, 50, 100, and 200 wt.%) in graphene oxide (GO) were varied to produce the various RGOHs. Upon irradiation with 80 kGy from γ-Ray, the successful reduction of GO occurred in the presence of hesperidin. The reduction process was confirmed by different characterization techniques such as FTIR, XRD, HRTEM, and Raman Spectroscopy. A cytotoxicity study using the MTT method was performed to evaluate the cytotoxic-anticancer effects of arbitrary RGOH on Wi38, CaCo2, and HepG2 cell lines. The assessment of RGOH's anti-inflammatory activity, including the monitoring of IL-1B and IL-6 activities as well as NF-kB gene expression was done. In addition, the anti-invasive and antimetastatic properties of RGOH, ICAM, and VCAM were assessed. Additionally, the expression of the MMP2-9 gene was quantified. The assessment of apoptotic activity was conducted by the detection of gene expressions related to BCl2 and P53. The documentation of the JNK/SMAD4/MMP2 signaling pathway was ultimately accomplished. The findings of our study indicate that RGOH therapy has significant inhibitory effects on the JNK/SMAD4/MMP2 pathway. This suggests that it could be a potential therapeutic option for cancer.
Asunto(s)
Rayos gamma , Grafito , Hesperidina , Metaloproteinasa 2 de la Matriz , Nanocompuestos , Proteína Smad4 , Humanos , Grafito/química , Grafito/farmacología , Nanocompuestos/química , Hesperidina/farmacología , Hesperidina/química , Proteína Smad4/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Tecnología Química Verde/métodos , Transducción de Señal/efectos de los fármacos , Células CACO-2 , Células Hep G2 , Línea Celular Tumoral , MAP Quinasa Quinasa 4/metabolismoRESUMEN
BACKGROUND: Duodenal ulcer (DU) is a common problem in patients with chronic liver disease (CLD) and with inadequate response to H2 receptor antagonists. Omeprazole might be more effective. In DU-CLD patients, Helicobacter pylori prevalence is low. Nitric oxide is increased in gastric mucosa in cirrhosis. Oxygen-free radicals have a role in gastric inflammation and are abnormal in CLD. Nitrotyrosine is a marker of nitric oxide and oxygen-free radical toxic mucosal reaction. METHODS: Sixty-nine patients were divided into 2 groups: control (26 patients with DU) and CLD groups (43 patients, DU-CLD). Omeprazole was given (40 mg/day) for 2 or 4 weeks. Symptoms and endoscopy findings were recorded before and after treatment. Antral biopsy specimens were stained for H. pylori and nitrotyrosine. RESULTS: Clinical features of DU are similar in patients with and without CLD. The main presentation was epigastric pain (70%) and bleeding (23%). Healing rate with omeprazole was higher in DU-CLD patients (90.7%) than in controls (80.8%). H. pylori was much lower in DU-CLD patients (51.2%) than controls (96.2%). Nitrotyrosine staining was negative in normal controls (0%) and positive in control-DU (100%), CLD-H. pylori positive (81%), and CLD-H. pylori negative (91%) cases. CONCLUSIONS: DU in patients with CLD is not different clinically from those without CLD. Omeprazole effectively and safely treats DU in CLD. Nitric oxide and free oxygen radicals may result in gastric mucosal changes in CLD similar to that caused by H. pylori.