Protective effect of Schisandra chinensis total lignans on acute alcoholic-induced liver injury related to inhibiting CYP2E1 activation and activating the Nrf2/ARE signaling pathway

ABSTRACT Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a well-known traditional Chinese medicine used mainly as a recipe for hepatoprotection. Modern researches have revealed that the hepatoprotection is related to its lignans and crude polysaccharide. In this study, we examined the effect and mechanism of S. chinensis total lignans on the liver injury induced by alcoholic. S. chinensis total lignans were extracted with ethanol extraction. The liver index, alanine aminotransferase and aspartate aminotransferase levels in serum of the rat culture supernatant were examined. The malondialdehyde level and superoxide dismutase activities in serum and liver tissue, and triacylglyceride content in liver tissue were tested. Western blot was conducted to determine cytochrome P450 2E1 expression in liver tissue of rats. The results showed that S. chinensis total lignans administration significantly inhibited alcohol-induced liver injury. In exploring the underlying mechanisms of S. chinensis total lignans action, we found that it significantly decreased Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), Glutamyl transpeptidase (γ-GT), reactive oxygen species (ROS) and malondialdehyde (MDA) level in livers/serum and inhibited the gene expression level of CYP2E1 in rat livers. The Nuclear factor erythroid-2 related factor 2 (Nrf2) gene expression and Nuclear factor erythroid-2 related factor 2 (Nrf2) protein nuclear transfer increased significantly, and significantly increased the expression of downstream target gene and protein heme oxygenase-1 (HO-1), Glutamate--cysteine ligase regulatory subunit (GCLM), NAD(P)H:quinine oxidoreductase 1 (NQO1). Moreover, S. chinensis total lignans decreased production of pro-inflammatory markers including Tumor Necrosis Factor-α (TNF-α), Interleukin-1beta (IL-1β) and Interleukin-6 (IL-6). In conclusion, these results suggested that the inhibition of alcohol-induced liver injury by S. chinensis total lignans is associated with its ability to inhibiting CYP2E1 activation and activating the Nrf2/Antioxidant response element(ARE) signaling pathway.

Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats

Abstract Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28thand 35thdays of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p<0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p<0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.

Comparison of propofol-based sedation regimens administered during colonoscopy / Comparación de protocolos de sedación basados en propofol para obtener sedación durante endoscopias

Background: The ideal sedative agent for endoscopic procedures should allow a rapid modification ofthe sedation level and should not have any adverse effects. Aim: To evaluate and compare the efficacy, safety, cost and patient satisfaction of some propofol-based sedation regimens administered during colonoscopy. Material and Methods: One hundred twenty one patients scheduled for elective outpatient colonoscopy with conscious sedation were randomized to four groups to evaluate the administration of dexmedetomidine, sufentanil, meperidine and midazolam in combination with propofol to maintain sedation during the procedure. Evaluated outcomes were efficacy, safety, cost and patient satisfaction of sedation procedures. Results: Patients receiving dexmedetomidine achieved a higher degree of sedation when compared with the other groups (p < 0.05). The lapse to recoverprotective reflexes and motor function, was significantly shorter in groups receiving dexmedetomidine or sufentanil than in groups receiving meperidine or midazolam (p < 0.05). Therewere no differences between groups in pre-sedation and post-sedation neurophysiologic performance, measured by the Trail MakingA and B tests. Conclusions: Sedation for endoscopy can be safely and effectively accomplished with low doses of propofol combined with dexmedetomidine, intranasal sufentanil, IV meperidine and IV meperidine with midazolam.

Antecedentes: El protocolo de sedación ideal para procedimientos endoscópi-cos es aquel que permita efectuar modificaciones rápidas del nivel de sedación y no tenga efectos secundarios. Objetivo: Comparar la eficacia, seguridad, costos y satisfacción del paciente con protocolos de sedación basados en propofol, durante colonoscopias. Material y Métodos: Ciento veinte pacientes programados para una colonoscopia fueron aleatorizados en cuatro grupos en que se evaluó la administración de dexmedetomidina, sufentanil, meperidina y midazolam en combinación con propofol, para mantener la sedación durante el procedimiento. Se evaluó la eficacia, seguridad, costo y satisfacción del paciente con los diferentes protocolos de sedación. Resultados: Los pacientes que recibieron dexmedetomidina, alcanzaron un mayor nivel de sedación que el resto de los grupos. El lapso necesario para recuperar reflejos y funciones motoras protectoras, fue significativamente menor en los grupos que recibieron dexmedetomidina o sufentanil comparado con los grupos que recibieron meperidina o midazolam (p < 0,05). No hubo diferencias entre los grupos en la capacidad neuro-cognitiva, medida con los Tests de Reitan A y B, antes o después de la sedación. Conclusiones: Se puede obtener una buena sedación para endoscopia combinando dosis bajas de propofol con dexmedetomidina, sufentanil intranasal, meperidina endovenosa con o sin midazolam.