ABSTRACT
Introduction: Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. Objective: We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Methods: Thirty rats were divided into three groups as sham (n=10), control (n=10) and thymoquinone (TQ) treatment group (n=10). Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Results: Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI). Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons). Conclusion: Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model. .
Introdução: Estudos prévios demonstraram que a timoquinona tem efeitos protetores contra a lesão de isquemia/reperfusão em vários órgãos como pulmão, rins e fígado em diferentes modelos experimentais. Objetivo: Determinar se timoquinona tem efeitos positivos em tecidos do pulmão, rim e coração e no estresse oxidativo em lesão de isquemia/perfusão da aorta abdominal. Métodos: Trinta ratos foram divididos em três grupos: sham (n=10), controle (n=10) e tratamento com timoquinona (TQ) (n=10). Os grupos controle e de tratamento com TQ foram submetidos à isquemia da aorta abdominal durante 45 minutos, seguido por um período de 120 minutos de reperfusão. No grupo de tratamento com TQ, a timoquinona foi administrada 5 minutos antes da reperfusão, dose de 20 mg/kg através da via intraperitoneal. A capacidade total antioxidante, estado oxidativo total (TOS) e o índice de estresse oxidativo (OSI) no soro do sangue foram medidos, e a histopatologia dos tecidos do pulmão, rim e coração foram avaliados com microscopia de luz. Resultados: Estado oxidativo e índice de estresse oxidativo total em amostras de sangue foram estatisticamente mais altos no grupo controle em relação aos grupos sham e tratamento com TQ (P<0,001 para TOS e OSI). Escores de lesões no grupo controle foram estatisticamente mais altos em relação aos grupos sham e tratamento com TQ (P<0,001 para todas as comparações). Conclusão: A timoquinona administrada por via intraperitoneal foi eficaz na redução do estresse oxidativo e lesão histopatológica em modelo de rato de isquemia/reperfusão aguda da aorta abdominal. .
Subject(s)
Animals , Humans , Mice , Endothelial Cells/enzymology , Glucagon-Like Peptide 1/pharmacology , Microvessels/cytology , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Recombinant Proteins/pharmacology , Signal Transduction/drug effects , Apoptosis/drug effects , Cell Line , Cell Proliferation/drug effects , Cyclic AMP/metabolism , Endothelial Cells/drug effects , Gene Expression/drug effects , Lipoproteins, LDL/pharmacologyABSTRACT
Background & objectives: Nutritional compounds which display anti-inflammatory and antioxidant effects have specific applications in preventing oxidative stress and endothelial dysfunction. In this study we evaluated the effect of Lisosan G (powder of Triticum sativum grains) on human microvascular endothelial cells (HMEC-1) exposed to oxidized low density lipoprotein (ox-LDL). Methods: The protective effects of Lisosan G were evaluated on human microvascular endothelial cells exposed to ox-LDL. Intercellular adhesion molecular-1 (ICAM-1), endothelin-1 (ET-1), and interleukin-6 (IL-6) concentrations and the expression of the respective genes were evaluated in response to incubation with ox-LDL, after co-incubation with ox-LDL and Lisosan G or exposed to Lisosan G alone. The analysis of LOX-1 gene was performed with RT-PCR semi quantitative method. The degree of oxidation induced in relation to control, was established by measurement of malondialdehyde (MDA) production. Results: The incubation with ox-LDL induced a significant increase in ICAM-1, IL-6 and ET-1 levels compared to the basal condition (P<0.01, P<0.05, and P<0.01, respectively), while in presence of Lisosan G, ICAM-1 levels showed a significant reduction both compared to the cultures treated with ox-LDL and control (P<0.01). IL-6 levels did not show any difference; ET-1 levels showed a partial reduction after co-treatment with Lisosan G, and also with Lisosan G alone, reduced the concentration below control (P<0.01). The modulation of these markers was confirmed by RT-PCR analysis. An association between MDA formation and the three markers production was observed. Semi-quantitative analysis of LOX-1 gene expression showed a significant up-regulation only after ox-LDL exposure. Interpretation & conclusions: The results demonstrate that Lisosan G may have an important role in the prevention of microcirculatory dysfunction.
Subject(s)
Analysis of Variance , Biomarkers/metabolism , Cell Line , Endothelial Cells/drug effects , Endothelial Cells/physiology , Endothelin-1/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Interleukin-6/metabolism , Lipoproteins, LDL/metabolism , Microcirculation/drug effects , Microcirculation/physiology , Microvessels/cytology , Plant Extracts/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Scavenger Receptors, Class E/metabolismABSTRACT
PURPOSE: Endothelial cells maintain the homeostasis of blood, which consists of plasma and cellular components, and regulate the interaction between blood and the surrounding tissues. They also have essential roles in vascular permeability, the circulation, coagulation, inflammation, wound healing, and tissue growth. The senescence of endothelial cells is closely related to the aging of the adjacent tissues and to age-related vascular disease. Recently, the expression of moesin was found to be decreased in elderly human dermal microvascular endothelial cells (HDMECs), and an association between moesin and senescence has been suggested. This study examined the functional role of moesin in cellular senescence. MATERIALS AND METHODS: To study the effects of decreased moesin expression on cellular senescence and metabolism, HDMECs were transfected with short hairpin-RNA (shRNA) lentivirus to silence moesin gene expression. In addition, specimens from young and old human skin were stained with anti-moesin and anti-p16 antibodies as an in vivo study. RESULTS: Using shRNAl-entivirus, moesin knock-down HDMECs developed characteristics associated with aging and expressed senescence associated-beta-galactosidase during early passages. They also showed increased p16 expression, decreased metabolic activity, and cell growth retardation. Human skin tissue from elderly persons showed decreased moesin expression and increased p16 expression. CONCLUSION: These findings suggest that there is a functional association between moesin expression and cellular senescence. Further study of the functional mechanism of moesin in the cytoskeleton and cellular senescence is needed. In addition, this study provides a useful model for developing anti-aging treatments.