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Background/objectives: The porcine intestinal epithelium plays a fundamental role as a defence interface against pathogens. Its alteration can cause severe inflammatory conditions and diseases. Hyperosmotic stress under physiological conditions and upon pathogen challenge can cause malabsorption. Different cell types counteract the osmolarity increase by accumulating organic osmolytes such as betaine, taurine, and myo-inositol through specific transporters. Betaine is known for protecting cells from hyperosmotic stress and has positive effects when fed to pigs. The aim of this study is to demonstrate the modulation of osmolyte transporters gene expression in IPEC-J2 during osmolarity changes and assess the effects of betaine. Methods: IPEC-J2 were seeded in transwells, where differentiate as a polarized monolayer. Epithelial cell integrity (TEER), oxidative stress (NO) and gene expression of osmolyte transporters, tight junction proteins (TJp) and pro-inflammatory cytokines were evaluated. Results: Cells treated with NaCl hyperosmolar medium (500 mOsm/L) showed a TEER decrease at 3 h and detachment within 24 h, associated with an osmolyte transporters reduction. IPEC-J2 treated with mannitol hyperosmolar medium (500 mOsm/L) upregulated taurine (TauT), myo-inositol (SMIT) and betaine (BGT1) transporters expression. A decrease in TJp expression was associated with a TEER decrease and an increase in TNFα, IL6, and IL8. Betaine could attenuate the hyperosmolarity-induced reduction in TEER and TJp expression, the NO increase and cytokines upregulation. Conclusions: This study demonstrates the expression of osmolyte transporters in IPEC-J2, which was upregulated upon hyperosmotic treatment. Betaine counteracts changes in intracellular osmolarity by contributing to maintaining the epithelial barrier function and reducing the inflammatory condition. Compatible osmolytes may provide beneficial effects in therapies for diseases characterized by inflammation and TJp-related dysfunctions. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. METHODS: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+K+-ATPase activity, in addition to histological analysis. RESULTS: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. CONCLUSION: Treatment of rats with betaine significantly restored GSH level and Na+K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue. [ABSTRACT FROM AUTHOR]

Hyperosmotic stress is an often overlooked process that potentially contributes to a number of human diseases. Whereas renal hyperosmolarity is a well-studied phenomenon, recent research provides evidence that many non-renal tissues routinely experience hyperosmotic stress that may contribute significantly to disease initiation and progression. Moreover, a growing body of evidence implicates hyperosmotic stress as a potent inflammatory stimulus by triggering pro-inflammatory cytokine release and inflammation. Under physiological conditions, the urine concentrating mechanism within the inner medullary region of the mammalian kidney exposes cells to high extracellular osmolarity. As such, renal cells have developed many adaptive strategies to compensate for increased osmolarity. Hyperosmotic stress is linked to many maladies, including acute and chronic, as well as local and systemic, inflammatory disorders. Hyperosmolarity triggers cell shrinkage, oxidative stress, protein carbonylation, mitochondrial depolarization, DNA damage, and cell cycle arrest, thus rendering cells susceptible to apoptosis. However, many adaptive mechanisms exist to counter the deleterious effects of hyperosmotic stress, including cytoskeletal rearrangement and up-regulation of antioxidant enzymes, transporters, and heat shock proteins. Osmolyte synthesis is also up-regulated and many of these compounds have been shown to reduce inflammation. The cytoprotective mechanisms and associated regulatory pathways that accompany the renal response to hyperosmolarity are found in many non-renal tissues, suggesting cells are commonly confronted with hyperosmotic conditions. Osmoadaptation allows cells to survive and function under potentially cytotoxic conditions. This review covers the pathological consequences of hyperosmotic stress in relation to disease and emphasizes the importance of considering hyperosmolarity in inflammation and disease progression. [ABSTRACT FROM AUTHOR]

Hypertonicity affects many parts of the immune system. Animal studies and experiments in isolated cell cultures show that hypertonicity reversibly suppresses several neutrophil functions and at the same time up-regulates T-lymphocyte function. Infusion of hypertonic saline with or without colloids may thus, besides providing efficient plasma volume expansion, ameliorate the detrimental consequences on the immune function of trauma, shock, reperfusion, and major surgery. However, the few clinical studies conducted to date, specifically addressing the immune effect of hypertonic saline infusion, have shown little, if any, effect on markers of immune function, and larger clinical trials have not demonstrated benefit in terms of morbidity or mortality. Thus, as opposed to animal and cell-culture studies, the immune-modulating properties of hypertonic saline infusion would appear to be of limited value in clinical practice. This review presents in vitro studies, animal experiments, and clinical trials which investigated the consequences of hypertonic saline on markers of immune function. [ABSTRACT FROM AUTHOR]

Many biological effects of taurine rely upon its cellular concentration, which is primarily controlled by taurine biosynthetic enzymes cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD) and taurine transporter (TauT). The cloning of CDO, CSD and Taut in various species provided first-hand information on these proteins, as well as molecular tools to investigate their regulations. CDO upregulation in hepatocytes in response to high sulfur amino acids appears clearly as the most spectacular among the regulations of the biosynthetic enzymes. Downregulation of Taut activity by activation of PKC appears particularly well documented. A unique serine residue could be identified as a phosphorylation site that leads to an inactive form of TauT. The previously revealed downregulation of Taut expression by taurine and hypertonicity-induced upregulation of Taut expression were shown to result from a modified transcription rate of Taut gene, but the precise molecular mechanisms are not yet formally established. Other regulations of taurine transporter expression were more recently reported, which involve glucose, tumor suppressor protein p53, tumor necrosis factor-α, and nitric oxid. This review reports the experimental models and data that support these various regulations but also points out the aspects that remain poorly understood or unknown concerning their molecular basis and physiological significance. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is a wound-healing response to chronic liver injury, which if persistent leads to cirrhosis and liver failure. Exciting progress has been made in understanding the mechanisms of hepatic fibrosis. Major advances include: (i) characterization of the components of extracellular matrix (ECM) in normal and fibrotic liver; (ii) identification of hepatic stellate cells as the primary source of ECM in liver fibrosis; (iii) elucidation of key cytokines, their cellular sources, modes of regulation, and signalling pathways involved in liver fibrogenesis; (iv) characterization of key matrix proteases and their inhibitors; (v) identification of apoptotic mediators in stellate cells and exploration of their roles during the resolution of liver injury. These advances have helped delineate a more comprehensive picture of liver fibrosis in which the central event is the activation of stellate cells, a transformation from quiescent vitamin A-rich cells to proliferative, fibrogenic and contractile myofibroblasts. The progress in understanding fibrogenic mechanisms brings the development of effective therapies closer to reality. In the future, targeting of stellate cells and fibrogenic mediators will be a mainstay of antifibrotic therapy. Points of therapeutic intervention may include: (i) removing the injurious stimuli; (ii) suppressing hepatic inflammation; (iii) down-regulating stellate cell activation; and (iv) promoting matrix degradation. The future prospects for effective antifibrotic treatment are more promising than ever for the millions of patients with chronic liver disease worldwide. [ABSTRACT FROM AUTHOR]