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

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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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Selenium, selenoproteins and human health: a review.

KM Brown, JR Arthur (2001)

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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Oxidant-antioxidant system: role and significance in human body.

M Irshad, P. Chaudhuri (2002)

Present article gives a holistic view of the causes, role and conrol of oxidative stress in the development and progression of various human diseases. Several types of reactive species are generated in the body as a result of metabolic reactions in the form of free radicals or non-radicals. These species may be either oxygen derived or nitrogen derived and called prooxidants. They attack macromolecules including protein, DNA and lipid etc. causing cellular/tissue damage. To counter their effect, the body is endowed with another category of compounds called antioxidants. These antioxidants are produced either endogenously or received from exogenous sources and include enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, minerals like Se, Mn, Cu and Zn, and vitamins like vitamin A, C and E. Other compounds with antioxidant activity include glutathione, flavonoids, bilirubin and uric acid etc.. In a healthy body, prooxidants and antioxidants maintain a ratio and a shift in this ratio towards prooxidants gives rise to oxidative stress. This oxidative stress may be either mild or severe depending on the extent of shift and remains the cause of several diseases such as cardiovascular diseases, neurological diseases, malignancies, renal diseases, diabetes, inflammatory problems, skin diseases, aging, respiratory diseases, liver diseases and different types of viral infections. As more and more reports are pouring in, a lot of information is being unfolded about oxidative stress in relation to several other diseases.

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Zinc, copper, and blood pressure: Human population studies

William E. Carpenter, Derek Lam, Glenn M. Toney … (2013)

Summary Copper and zinc are essential trace biometals that regulate cardiovascular homeostasis, and dysregulation of these metals has been linked to vascular diseases, including hypertension. In this article, we review recent human population studies concerning this topic, focusing on: 1) the relationship between blood pressure and levels of zinc and copper; 2) correlations between trace metals, the renin-angiotensin system, obesity, and hypertension; 3) the relationship between environmental metal pollution and the development of hypertension; and 4) methods commonly employed to assay zinc and copper in human specimens. Moreover, based on the findings of these studies, we suggest the following topics as the basis for future investigations: 1) the potential role of environmental metal pollution as a causal factor for hypertension; 2) metal profiles within specific pathogenic subsets of patients with hypertension; 3) standardizing the experimental design so that the results between different studies are more comparable; and 4) the requirement for animal experiments as complementary approaches to address mechanistic insight that cannot be studied in human populations.