RESUMEN
Monosodium glutamate (MSG) is the sodium compound derived from glutamic acid. Excessive daily ingestion of MSG leads to elevated amounts of glutamic acid in the bloodstream, which can be detrimental to brain structures. Camellia sinensis, often known as green tea (GT), is a rich source of essential hexogen antioxidants that are necessary for the body. Thirty-two adult male albino rats were divided into four groups (n = 8). Group 1 served as a control -ve group. Group 2 was given GT (1.5 ml/rat/day). Group 3 was given MSG (600 mg/kg/day). Group 4 was given MSG (600 mg/kg/day) and GT (1.5 ml/rat/day). All treatments were given orally for 28 days. MSG administration resulted in significant neurotoxicity in rats that was revealed by the significant reduction of serum concentration of glutathione peroxidase (GPx) and nitric oxide (NO), and the significant elevation of total antioxidant capacity (TAC) accompanied by the significant reduction of levels of serum monoamines (dopamine, serotonin, and norepinephrine) and histological changes in the hippocampus area CA1, dentate gyrus, and cerebellar cortex and positive immunohistochemical staining of glial fibrillary acidic proteins (GFAP) and calretinin. Administration of GT with MSG counteracted the MSG-mediated oxidative stress by significantly increasing serum concentrations of GPX and NO and significantly decreasing concentrations of TAC. Furthermore, GT significantly increased levels of serum monoamines (dopamine, serotonin, and norepinephrine). Moreover, it ameliorated the histological changes, GFAP, and calretinin immunostaining in brain tissues. It is envisaged that GT will serve as a viable protective choice for the inclusion of the neurotoxicity treatment procedure.
Asunto(s)
Antioxidantes , Camellia sinensis , Síndromes de Neurotoxicidad , Glutamato de Sodio , Animales , Glutamato de Sodio/toxicidad , Masculino , Camellia sinensis/química , Ratas , Síndromes de Neurotoxicidad/prevención & control , Síndromes de Neurotoxicidad/tratamiento farmacológico , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Glutatión Peroxidasa/metabolismo , Óxido Nítrico/metabolismo , Ratas WistarRESUMEN
Sustained inflammatory responses can badly affect several vital organs and lead to chronic inflammation-related disorders, such as atherosclerosis, pneumonia, rheumatoid arthritis, obesity, diabetes, Alzheimer's disease, and cancers. Salvia multicaulis is one of the widely distributed plants that contains several biologically active phytochemicals and diterpenoids with anti-inflammatory effects. Therefore, finding alternative and safer natural plant-extracted compounds with good curative anti-inflammatory efficiencies is an urgent need for the clinical treatment of inflammation-related diseases. In the current study, S. multicaulis Vahl was used to extract and isolate two compounds identified as salvimulticanol and candesalvone B methyl ester to examine their effects against inflammation in murine macrophage RAW264.7 cells that were induced by lipopolysaccharide (LPS). Accordingly, after culturing RAW264.7 cells and induction of inflammation by LPS (100 ng/ml), cells were exposed to different concentrations (9, 18, 37.5, 75, and 150 µM) of each compound. Then, Griess assay for detection of nitric oxide (NO) levels and western blotting for the determination of inducible nitric oxide synthase (iNOS) expression were performed. Molecular docking and molecular dynamics (MD) simulation studies were employed to investigate the anti-inflammatory mechanism. Our obtained results validated that the level of NO was significantly decreased in the macrophage cell suspensions as a response to salvimulticanol treatment in a dose-dependent manner (IC50: 25.1 ± 1.2 µM) as compared to the methyl ester of candesalvone B which exerted a weaker inhibition (IC50: 69.2 ± 3.0 µM). This decline in NO percentage was comparable with a down-regulation of iNOS expression by western blotting. Salvimulticanol strongly interacted with both the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex and the inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKß) to disrupt their inflammatory activation due to the significant hydrogen bonds and effective interactions with amino acid residues present in the target proteins' active sites. S.multicaulis is a rich natural source of the aromatic abietane diterpenoid, salvimulticanol, which exerted a strong anti-inflammatory effect through targeting iNOS and diminishing NO production in LPS-induced RAW264.7 cells in a mechanism that is dependent on the inhibition of TLR4-MD-2 and IKKß as activators of the classical NF-κB-mediated inflammatory pathway.
RESUMEN
BACKGROUND: Poisoning-induced shock is a serious medical emergency with a high mortality rate. Hospitalized poisoned individuals experience multiple adverse cardiovascular events that could progress to cardiac arrest. This study was designed to compare the prognostic role of the admission shock index and plasma copeptin level in shocked poisoned patients and to evaluate their associations with initial patients' characteristics and outcomes. METHODS: We conducted a prospective study on acutely poisoned adult patients. RESULTS: A total of 41 patients were enrolled in the study. The mean age of all patients was 27.05 ± 10.99 years and most of the patients were females (n = 27, 66%). Pesticides were the most common type of poisoning (n = 18, 44%), followed by cardiovascular drugs (n = 12, 29.3%). Eleven (26.8%) patients died during the hospital stay length. The initial serum copeptin level and shock index could predict organ dysfunction indexed by sequential organ assessment score (SOFA) with area under the curve (AUCs) of 0.862 and 0.755, respectively. Initial serum copeptin and lactate levels, SOFA score, and their combination can strongly differentiate between survivors and non-survivors with an AUC of 0.944, 0.885, and 0.959, and 0.994, respectively. CONCLUSION: We concluded that the shock index, serum lactate level, and SOFA score may help in risk stratifying patients and predicting outcomes in critically ill patients with poisoning-induced shock. Copeptin is superior to the shock index in predicting mortality among the studied patients. However, a combination of SOFA score, serum copeptin level, and serum lactate level can develop a more predominant prediction for overall clinical outcomes in these patients.