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Effect of deferiprone plus taurine on the antioxidant system, ATPase levels, and metal ion levels in rat livers exposed to aluminum

Trace Elements and Electrolytes

Dustri-Verlag Dr. Karl Feistle

aluminum, antioxidant system, DFP, ATPase, taurine


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      Abstract

      Abstract. Objectives: To evaluate the protective effect of the chelating agent deferiprone (DFP) with and without taurine (Tau) against aluminum (Al)-induced liver toxicity. Method: 56 male Wistar rats were randomly divided into seven groups: control, Al-treated, low-dose DFP, high-dose DFP, Tau + low-dose DFP and Tau + high-dose DFP. The control group received 1 mL/kg/day saline solution for 8 weeks. The other groups were exposed to Al at a dose of 281.40 mg/kg/day orally for 4 weeks. Then, they were administered with 1 mL/kg/day saline solution, 400 mg/(kg×day) Tau, 13.82 mg/(kg×day) DFP, 27.44 mg/(kg×day) DFP, 400 mg/(kg×day) Tau +13.82 mg/(kg×day) DFP, and 400 mg/(kg×day) Tau +27.44 mg/(kg×day) DFP for 4 weeks. After that, the changes in markers of oxidative stress, activities of antioxidant enzymes, triphosphatase (ATPase) in the liver and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were determined. Al and iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), and magnesium (Mg) were determined by atomic absorption spectrophotometry. Results: Serum ALT, AST, and liver malondialdehyde (MDA) were significantly higher after Al intake, while the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and ATPases were significantly lower compared with the control group (p < 0.05). Al and Cu concentrations in the liver were higher and Fe and Zn concentrations were lower in Al-treated rats (p < 0.05). Treatment with DFP or Tau alone restored MDA, Al, and Fe levels, and activities of GSH-Px, ALT, Na + K + -ATPase, and Mg 2+ -ATPase to control levels (p < 0.05). Combined DFP and Tau treatment was more effective than DFP or Tau alone (p < 0.05). Conclusion: Combined DFP and Tau treatment alleviated oxidative stress and improved liver function more effectively than DFP alone.


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      Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury.

      This study determines whether acid-base data obtained in the emergency department correlate with outcome from major vascular injury. Observational, retrospective record review of trauma patients requiring vascular repair (torso or extremity, January 1988 to December 1997). Data included age, Injury Severity Score, injury mechanism, survival, laboratory profiling, calculated anion gap, strong ion difference, and strong ion gap. Patients were divided into survivors and nonsurvivors with comparison by Student's t-test; significance was assumed for p or = 5 mmol/L, and strong ion gap > or = 5 mEq/L. All of the acid-base descriptors were strongly associated with outcome, but the strong ion gap discriminated most strongly with an area under the receiver operator characteristic of 0.991 (95% confidence interval, 0.972-0.998). The initial emergency department acid-base variables of pH, base deficit, lactate, anion gap, apparent strong ion difference, and strong ion gap discriminate survivors from non-survivors of major vascular injury. The strong ion gap is most strongly predictive of mortality following major vascular trauma.
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        Selenium, selenoproteins and human health: a review.

        Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.
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          The value of the chloride: sodium ratio in differentiating the aetiology of metabolic acidosis.

          Stewart's physicochemical approach to acid-base balance defines the aetiology of a metabolic acidosis by quantifying anions of tissue acids (TA), which consist of unmeasured anions (UMA) and/or lactate. We hypothesised that an increase in TA during metabolic acidosis would lead to a compensatory fall in the plasma chloride (Cl) relative to sodium (Cl:Na ratio) in order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used as a simple alternative to the anion gap in identifying raised TA. Two hundred and eighty two consecutive patients who were admitted to our Paediatric Intensive Care were enrolled in the study. We obtained 540 samples (admission n = 282, 24 h n = 258) for analysis of blood chemistry, lactate and quantification of TA and UMA. Samples were subgrouped into those with metabolic acidosis (standard bicarbonate 3 mEq/l). Metabolic acidosis occurred in 46% of samples, of which 52.3% (120/230) had increased UMA. The dominant component of TA was UMA rather than lactate, and these two components did not always rise in tandem. Our hypothesis of relative hypochloraemia was supported by a lower Cl:Na ratio (P 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate performed poorly. In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.
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