RESUMEN
INTRODUCTION AND AIM: Stevia has exhibited antioxidant, antihyperglycemic, antihypertensive and anti-inflammatory properties in several in vivo and in vitro models. The objective of this study was to investigate the ability of an aqueous extract of stevia (AES) to prevent experimental cirrhosis in rats and to explore its mechanism of action. MATERIALS AND METHODS: Liver cirrhosis was induced by administering carbon tetrachloride (CCl4) (400mg/kg by i.p. injection 3 times a week for 12 weeks); AES was administered (100mg/kg by gavage daily) during the CCl4 treatment. Fibrosis was evaluated with histological, biochemical and molecular approaches, and liver damage was assessed with standardized procedures. The profibrotic pathways were analyzed by western blotting, qRT-PCR and immunohistochemistry. RESULTS AND CONCLUSIONS: Chronic CCl4 administration increased nuclear factor kappa B (NF-κB) and proinflammatory cytokine production as well as oxidative parameters such as lipid peroxidation and 4-hydroxynonenal levels, whereas GSH and nuclear factor-E2-related factor 2 (Nrf2) levels were decreased. CCl4 induced profibrogenic mediator expression, hepatic stellate cell (HSC) activation and, consequently, extracellular matrix production. AES exhibited antioxidant, anti-inflammatory and antifibrotic properties, probably because of its capacity to induce Nrf2 expression, reduce NF-κB expression and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis induced by chronic CCl4 administration.
Asunto(s)
Cirrosis Hepática Experimental/prevención & control , Hígado/patología , Estrés Oxidativo , Extractos Vegetales/farmacología , Stevia , Animales , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratas , Ratas Wistar , Edulcorantes/farmacologíaRESUMEN
Stevia has been shown to prevent oxidative stress and inflammation in carbon tetrachlorideinduced cirrhosis models. This study aimed to investigate the ability of an aqueous extract of stevia (AES) to prevent thioacetamide (TAA)induced cirrhosis in rats and to explore its mechanism of action. Liver cirrhosis was established by administering TAA (200 mg/kg by i.p. injections three times a week for 10 weeks); AES was administered (100 mg/kg by gavage daily) during the TAA treatment. Liver damage and fibrosis were evaluated, and the profibrotic pathways were analyzed by western blotting and immunohistochemistry. TAA increased nuclear factor kappa B (NFκB) and proinflammatory cytokine production, as well as the malondialdehyde and 4hydroxynonenal levels, whereas the glutathione/glutathione disulfide and nuclear factorE2related factor 2 (Nrf2) levels were decreased. Moreover, TAA increased collagen production, hepatic stellate cell (HSC) activation, and expression of profibrogenic mediators. TAAtreated rats that had been exposed to Mn2+ exhibited altered striatal dopamine turnover, indicating hepatic encephalopathy. AES partially or completely prevented all of these effects. AES showed antioxidant, antiinflammatory, and antifibrotic properties, probably because of its capacity to induce Nrf2 expression, reduce NFκB expression, and block several profibrogenic signaling pathways, subsequently inhibiting HSC activation and preventing fibrosis and dopamine turnover.
Asunto(s)
Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática Experimental/prevención & control , Factor 2 Relacionado con NF-E2/fisiología , FN-kappa B/fisiología , Extractos Vegetales/uso terapéutico , Proteína smad7/fisiología , Stevia , Factor de Crecimiento Transformador beta/fisiología , Animales , Células Estrelladas Hepáticas/fisiología , Cirrosis Hepática Experimental/inducido químicamente , Masculino , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , TioacetamidaRESUMEN
Trophozoites of Entamoeba histolytica HM-1:IMSS become less virulent after long-term maintenance in axenic cultures. The factors responsible for the loss of virulence during in vitro cultivation remain unclear. However, it is known that in vitro cultivation of amoeba in culture medium supplemented with cholesterol restores their virulence. In this study, we analyzed the effect of adding phosphatidylcholine-cholesterol (PC-Chol) liposomes to the culture medium and evaluated the effect of this lipid on various biochemical and biological functions of E. histolytica HM-1:IMSS in terms of its virulence. The addition of PC-Chol liposomes to the culture medium maintained the virulence of these parasites against hamster liver at the same level as the original virulent E. histolytica strain, even though these amoebae were maintained without passage through hamster liver for 18 months. The trophozoites also showed increased endocytosis, erythrophagocytosis, and carbohydrate residue expression on the amoebic surface. Protease activities were also modified by the presence of cholesterol in the culture medium. These findings indicate the capacity of cholesterol to preserve amoeba virulence and provide an alternative method for the maintenance of virulent E. histolytica trophozoites without the need for in vivo procedures.