RESUMEN
SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process.
RESUMEN
Mitochondrial dysfunction plays a key role in the development of neurodegenerative disorders. In contrast, the regulation of the endocannabinoid system has been shown to promote neuroprotection in different neurotoxic paradigms. The existence of an active form of the cannabinoid receptor 1 (CB1R) in mitochondrial membranes (mitCB1R), which might exert its effects through the same signaling mechanisms as the cell membrane CB1R, has been shown to regulate mitochondrial activity. Although there is evidence suggesting that some cannabinoids may induce protective effects on isolated mitochondria, substantial evidence on the role of cannabinoids in mitochondria remains to be explored. In this work, we developed a toxic model of mitochondrial dysfunction induced by exposure of brain mitochondria to the succinate dehydrogenase inhibitor 3-nitropropionic acid (3-NP). Mitochondria were also pre-incubated with the endogenous agonist anandamide (AEA) and the synthetic CB1R agonist WIN 55212-2 to evaluate their protective effects. Mitochondrial reduction capacity, reactive oxygen species (ROS) formation, and mitochondrial swelling were assessed as toxic markers. While 3-NP decreased the mitochondrial reduction capacity and augmented mitochondrial ROS formation and swelling, both AEA and WIN 55212-2 ameliorated these toxic effects. To explore the possible involvement of mitCB1R activation on the protective effects of AEA and WIN 55212-2, mitochondria were also pre-incubated in the presence of the selective CB1R antagonist AM281, which completely reverted the protective effects of the cannabinoids to levels similar to those evoked by 3-NP. These results show partial protective effects of cannabinoids, suggesting that mitCB1R activation may be involved in the recovery of compromised mitochondrial activity, related to reduction of ROS formation and further prevention of mitochondrial swelling.
Asunto(s)
Ácidos Araquidónicos , Benzoxazinas , Encéfalo , Endocannabinoides , Mitocondrias , Morfolinas , Naftalenos , Fármacos Neuroprotectores , Nitrocompuestos , Alcamidas Poliinsaturadas , Propionatos , Ratas Wistar , Especies Reactivas de Oxígeno , Animales , Nitrocompuestos/toxicidad , Propionatos/farmacología , Propionatos/toxicidad , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Endocannabinoides/metabolismo , Endocannabinoides/farmacología , Benzoxazinas/farmacología , Ácidos Araquidónicos/farmacología , Morfolinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Alcamidas Poliinsaturadas/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Masculino , Fármacos Neuroprotectores/farmacología , Naftalenos/farmacología , Dilatación Mitocondrial/efectos de los fármacos , Ratas , Receptor Cannabinoide CB1/metabolismoRESUMEN
The extremotolerant red yeast Rhodotorula mucilaginosa displays resilience to diverse environmental stressors, including cold, osmolarity, salinity, and oligotrophic conditions. Particularly, this yeast exhibits a remarkable ability to accumulate lipids and carotenoids in response to stress conditions. However, research into lipid biosynthesis has been hampered by limited genetic tools and a scarcity of studies on adaptive responses to nutrient stressors stimulating lipogenesis. This study investigated the impact of nitrogen stress on the adaptive response in Antarctic yeast R. mucilaginosa M94C9. Varied nitrogen availability reveals a nitrogen-dependent modulation of biomass and lipid droplet production, accompanied by significant ultrastructural changes to withstand nitrogen starvation. In silico analysis identifies open reading frames of genes encoding key lipogenesis enzymes, including acetyl-CoA carboxylase (Acc1), fatty acid synthases 1 and 2 (Fas1/Fas2), and acyl-CoA diacylglycerol O-acyltransferase 1 (Dga1). Further investigation into the expression profiles of RmACC1, RmFAS1, RmFAS2, and RmDGA1 genes under nitrogen stress revealed that the prolonged up-regulation of the RmDGA1 gene is a molecular indicator of lipogenesis. Subsequent fatty acid profiling unveiled an accumulation of oleic and palmitic acids under nitrogen limitation during the stationary phase. This investigation enhances our understanding of nitrogen stress adaptation and lipid biosynthesis, offering valuable insights into R. mucilaginosa M94C9 for potential industrial applications in the future.
RESUMEN
Context: Chilean black-berry Aristotelia chilensis is a wild fruit that grows in Southern Chile. This fruit possesses a strong antioxidant activity and is commonly used in foods and beverages in Chile. Objective: The gastroprotective and anti-inflammatory activities of the extracts, fractions and subfractions as carrageenan induced paw oedema in rats are reported here for the first time. Materials and methods: Extracts, fractions, subfractions and several compounds werer used for measuring the effects in carrageenan-induced paw oedema inflammation of rat model and the gastroprotective activity was analyzed. Results: The results showed that extract B, fraction F-4, and ovatofolin, quercetin, myricetin, luteolin and diosmetin used as pattern compounds were the most active samples together with those subfractions rich in aglycone and phenolic compounds. Thus, SF11-SF15, SF16-SF20, and SF21-SF25 showed the best subfractions inhibitors in similar form to indomethacin, a known selective COX inhibitor. Results demonstrated that these samples strongly inhibited the carrageenan-induced inflammation in paw of the rat oedema model. Discussion and conclusion: These findings demonstrate that the fruits and their constituents of A. chilensis are anti-inflammatory and gastroprotective and thus have grat potential nutraceuticals.
Contexto: Chilean Black-berry Aristotelia chilensis es un fruto silvestre que crece en el sur de Chile. Este fruto posee uan fuerte actividad antioxidante y comúnmente es usado en alimentos y bebidas en Chile. Objetivo: Se investigó la actividad anti-inflamatoria y gastroprotectora de los extractos, fracciones y subfracciones de este fruto y son informados aquí por primera vez. Materiales y métodos: Los extractos, fracciones y subfracciones fueron analizados por su efecto sobre la inflamación en pata de rata a través de la inducción con carragenina en dosis sencillas. Además se investigó la actividad gastroprotectora sobre la mucosa del estómago de rata. Resultados: Los resultados muestran que el extracto B, la fracción F-3, F4 y ovatifolina, quercetina, myricetina, luteolina y diosmetina que se usaron como muestras patrones, fueron las más activas junto con aquellas subfracciones ricas en compuestos fenólicos. Así SF11-SF15, SF16-SF20, y SF21-SF25 mostraron ser las mejores subfracciones inhibitorias en una forma similar a indometacina en conocido inhibidor selectivo de COX. Los resultados demuestran que estas muestras inhiben fuertemente la inflamación inducida en el modelo del edema de pata de rata. Discusión y conclusión. Estos hallazgos demuestran que los frutos y sus constituyentes de A. chilensis poseen una excelente actividad anti-inflamatoria y gastroprotectora, y así tienen un gran potencial como una fuente de productos naturales saludables. Adicionalmente, estos hallazgos muestran que los flavonoides, ácidos fenólicos y antiocianinas presentes en este fruto podrían ser los responsables de la actividad nutracéutica.