ABSTRACT
Excessive consumption of carbohydrate and fat increases the risk of liver disease. We hypothesized that swim exercise can protect hepatocytes from ultra-structural damage induced by high cholesterol and fructose diets (HCFD). Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. Swim exercise trained rats started the treatment from the 11th week until the sacrifice day, end of week 15. Blood samples were assayed for biomarkers of liver injury and adiponectin. The harvested liver tissues were examined using transmission electron microscopy (TEM). TEM images revealed substantial damage and accumulation of lipid droplets (steatosis) in the hepatocytes of the model group that was inhibited by swim exercise. In addition, HCFD significantly (p < 0.0005) increased insulin resistance index (HOMA-IR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), which were effectively (p < 0.02) decreased by a swim exercise to levels comparable to control group. Whereas, swim exercise increased adiponectin levels in HCFD group (p < 0.03). These results show that HCFD-induced hepatic injury is ameliorated by swim training exercise possibly via restoration of a normal blood sugar and lipid, induction of adiponectin and inhibition of inflammatory, and liver injury biomarkers.
Subject(s)
Diet, High-Fat/adverse effects , Fructose/toxicity , Hepatocytes/ultrastructure , Non-alcoholic Fatty Liver Disease , Physical Conditioning, Animal/physiology , Animals , Blood Glucose , Fructose/administration & dosage , Hepatocytes/pathology , Insulin Resistance , Microscopy, Electron, Transmission , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/physiopathology , Non-alcoholic Fatty Liver Disease/prevention & control , Random Allocation , Rats , Rats, Sprague-Dawley , SwimmingABSTRACT
OBJECTIVES: Root resorption is a ubiquitous although undesirable sequela to orthodontic treatment. Current methods to investigate the pathophysiology have certain limitations. In pursuit to understand and develop treatment modalities for orthodontically induced root resorption, the ability to manipulate cells within their natural extracellular matrix in a three dimensional organotypic model is invaluable. The study aimed to develop a laboratory-based organotypic model to investigate the effect of orthodontic forces on the periodontium. METHODS: Mandibular slices of male Wistar rats were maintained in Trowel-typed cultures at 37°C in 5% carbon dioxide in air for 7 days with test specimens subjected to compressive forces at 50 g and 100g by stainless steel springs. Tissue architecture and cell viability were maintained under culture conditions. RESULTS: Osteoclast numbers increased significantly in both test groups whilst odontoclasts increased in the 50 g group. Immunohistochemistry demonstrated increased dentine sialoprotein expression in both test groups, suggesting changes in mineralization-related activity due to mechanical strain. CONCLUSION: The study showed initial cellular and molecular changes of key markers that relate to root resorption in response to mechanical loading. CLINICAL SIGNIFICANCE: Severe root resorption may occur when forces applied are heavy or transmitted over an extended period and could lead to mobility and tooth loss. This ex vivo model can be used to investigate cellular and molecular processes during orthodontic tooth movement which may advance the clinical management of root resorption.
Subject(s)
Root Resorption/etiology , Tooth Movement Techniques/instrumentation , Acid Phosphatase/analysis , Animals , Biomarkers/analysis , Biomechanical Phenomena , Bone Marrow/anatomy & histology , Bone Marrow/pathology , Cell Count , Cell Survival/physiology , Dental Pulp/anatomy & histology , Disease Models, Animal , Extracellular Matrix Proteins/analysis , Immunohistochemistry , Isoenzymes/analysis , Male , Mandible/anatomy & histology , Mandible/cytology , Organ Culture Techniques , Orthodontic Wires , Osteoclasts/classification , Osteoclasts/pathology , Periodontal Ligament/anatomy & histology , Periodontal Ligament/cytology , Phosphoproteins/analysis , Rats , Rats, Wistar , Root Resorption/pathology , Sialoglycoproteins/analysis , Stress, Mechanical , Tartrate-Resistant Acid PhosphataseABSTRACT
Previously, we reported that PC12 cells showed increased vulnerability to oxidative stress (OS) induced by H2O2 (as assessed by decrements in calcium recovery, i.e., the ability of cells to buffer Ca(2+) after a depolarization event) when the membrane levels of cholesterol (CHL) and sphingomyelin (SPH) were modified to approximate those seen in the neuronal membranes of old animals. The present study was designed to examine whether the enrichment of the membranes with SPH-CHL and increased cellular vulnerability to OS are mediated by neutral SPH-specific phospholipase C (N-Sase) and the intracellular antioxidant GSH. The results showed a significant up-regulation of N-Sase activity by both low (5 microM) and high (300 microM) doses of H2O2. However, under high doses of H2O2 the up-regulation of N-Sase is accompanied by a significant increase in reactive oxygen species and by a decrease in intracellular GSH. The enrichment of membranes with SPH-CHL significantly potentiated the effects of high doses of H2O2, by further reducing the intracellular GSH and further up-regulating the N-Sase activity. Furthermore, repleting intracellular GSH with 20 mM N-acetylcysteine treatment was sufficient to attenuate the effect of a low dose of H2O2 on Ca(2+) recovery in SPH-CHL-treated cells. Thus, these results suggested that age-related alterations in the membrane SPH-CHL levels could be important determinants of the susceptibility of neuronal cells to OS.
