RESUMEN
Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to prevent cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr in experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 h, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔÑ°m) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔÑ°m caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.
Asunto(s)
Canavalia , Pancreatitis , Enfermedad Aguda , Animales , Antiinflamatorios , Canavalia/química , Lectinas/farmacología , Masculino , Ratones , Necrosis/tratamiento farmacológico , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Lectinas de Plantas/química , Semillas/químicaRESUMEN
BACKGROUND: Prolonged exposure of free radicals, or known as reactive oxygen species (ROS), in hepatic cells may cause oxidative stress. Without proper treatment, it can induce liver injury and fatal hepatic disease, including cirrhosis. Red betel (Piper crocatum Ruiz and Pav) is one of Indonesia's medicinal plants that has been known to exhibit antioxidant, anti-inflammatory activities. This study aims to determine hepatoprotective effect of red betel leaves extract (RBLE) towards liver injury. METHOD: Hydrogen peroxide-induced HepG2 cells were used as liver injury model·H2O2-induced HepG2 cells were treated with 25 µg/mL and 100 µg/mL RBLE. Several parameters were observed, including TNF-α level through ELISA; necrotic, apoptotic, dead, live cells; and ROS level through flow cytometry analysis; and GPX gene expression through qPCR. RESULT: The study showed that treatment with RBLE were able to decrease TNF-α level; necrotic and death cells percentage; as well as ROS level. On the other hand, it were able to increase apoptotic and live cells percentage; as well as GPX gene expression. Low concentration (25 µg/mL) of RBLE treatment exhibited stronger anti-inflammatory activity as it was resulted in the lower TNF-α level and were able to switched hepatic cell death pathway from necrosis to apoptosis as shown by the shifted of apoptotic cells and necrotic cells percentage. This lead to lower death cells and ultimately improve live cells percentage. Meanwhile high concentration of RBLE (100 µg/mL) exhibited stronger antioxidant properties as indicated by lower ROS level and higher GPX gene expression. CONCLUSION: Overall, this study was able to demonstrate hepatoprotective effect of RBLE towards liver injury model through its anti-inflammatory and antioxidant activities.
RESUMEN
Liver diseases are serious life-threating conditions that should be controlled. Here, we identify a protein fraction from royal-jelly (RJ) that represents the most effective composite against CCl4-induced hepatotoxicity and HepG2 cell growth. Two closely related proteins were purified from this fraction by a new simple method and identified by MALDI-TOF MS as major RJ protein 2 (MRJP2) and its predicted isoform X1. The in silico assessment (3D structures and functions) of these proteins were performed using Iterative Threading ASSEmbly Refinement (I-TASSER) analysis and RAMPAGE program. These two purified proteins were able to relieve the necrotic hepatocytes (by 60.4%) via reducing tumor necrosis factor (TNF)-α, mixed lineage kinase domain-like protein (MLKL) and intracellular reactive species. The latter effects associated with improving hepatocyte functions. Furthermore, they revealed the potent anticancer effect via induction of caspase-dependent apoptosis and controlling the expression of both Bcl-2 and p53 in HepG2 cells. Thus, MRJP2 and its isoform X1 can be a promising dual strategy for fighting hepatic injury and cancer in future animal and human studies.
Asunto(s)
Citoprotección/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Proteínas de Insectos/farmacología , Secuencia de Aminoácidos , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Proteínas de Insectos/química , Proteínas de Insectos/aislamiento & purificación , Antígeno Ki-67/metabolismo , Masculino , Modelos Moleculares , Necrosis/patología , Conformación Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/aislamiento & purificación , Isoformas de Proteínas/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
BACKGROUND & OBJECTIVE: Heat Shock Proteins (HSPs) increase response to many stresses in cells. Stroke is a neural shock that leads to the destruction of a large number of brain cells, whereas induction and expression of HSPs can decrease the amount of damage, and in some conditions can cure damaged cells. HSP70 family is considered as the most important member of HSPs in normal and stress condition of cells. They are strongly up-regulated by stresses and have protective roles in under stressed cells. Therefore, in this review, we briefly consider the association between HSP70 and stroke. We searched in Pubmed and Scopus databases using the specified keywords and selected the articles based on the certain association between HSP70 and stroke. HSP70 protects cells from damage through a variety of cellular and biochemical processes such as chaperone function, anti-apoptotic, anti-necrotic and anti-inflammatory mechanisms. CONCLUSION: Protective effects of HSP70 in neurodegenerative shocks are illustrated in the review, and it can be concluded that the induction of HSP70 in stresses can be considered as a therapeutic factor, although it needs further studies.