Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.

Paraquat Poisonings: Mechanisms of Lung Toxicity, Clinical Features, and Treatment

▪ Abstract Mammalian selenium-containing proteins can be divided into three groups: proteins containing nonspecifically incorporated selenium, specific selenium-binding proteins, and specific selenocysteine-containing selenoproteins Selenoproteins with known functions identified so far include five glutathione peroxidases, two deiodinases, several thioredoxin reductases, and selenophosphate synthetase 2 Alternative splicing leads to a greater variety of selenoproteins, as was shown in the cases of a specific sperm nuclei glutathione peroxidase and some thioredoxin reductases Selenoprotein P, selenoprotein W, a 15-kDa selenoprotein, an 18-kDa selenoprotein, and several selenoproteins identified in silico from nucleotide sequence databases were found to contain selenocysteine but their functions are not known Gel electrophoretic separation of tissue samples from rats labeled in vivo with 75Se showed the existence of further selenium-containing proteins

Mammalian selenium-containing proteins.

Evidence for specific selenium target tissues and new biologically important selenoproteins

Selenium (Se) is a potent nutritional antioxidant that carries out biological effects through its incorporation into selenoproteins. Given the crucial roles that selenoproteins play in regulating reactive oxygen species (ROS) and redox status in nearly all tissues, it is not surprising that dietary Se strongly influences inflammation and immune responses. The notion that Se "boosts" the immune system has been supported by studies involving aging immunity or protection against certain pathogens. However, studies examining the effects of Se status on other types of immunity such as antiparasitic responses or allergic asthma have suggested more Se may not always be beneficial. In this review, we summarize and compare the available data regarding how the levels of Se affect different types of immunity. Overall, determining how Se intake differentially affects various types of immune responses and dissecting the mechanisms by which this occurs will lead to a better utilization of Se-supplementation for human diseases involving the immune system.

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The influence of selenium on immune responses.

In July, 1988, more than 300 scientists from 29 different countries gathered at Tiibingen, W. Germany, in order to spend 4 days discussing their favourite trace element, selenium. This meeting continued the good tradition of three previous meetings held in Corvallis/Oregon, 1976, in Lubbock/Texas, 1980, and in Beijing/China, in 1984. Incidentally, the University of Tiibingen provided a unique historical background for a Symposium devoted to recent advances in biochemistry, pharmacology, human nutrition and human health; here, the first independent depart ment of Physiological Chemistry in Germany was founded in 1845. Pro fessor H9Ppe-Seyler elucidated here the hemin structure and his student Friedrich Miescher discovered the nucleic acids. This book contains one-half of the oral or poster presentations which were selected before the meeting was held on the basis of a one page abstract. It is the reader who will have to decide whether this time consuming policy of quality assessment was warranted or not."

Selenium in biology and medicine

The selenium content was determined in the adrenals, brain, erythrocytes, femur, hair, heart, kidneys, lungs, muscle, pancreas, plasma, spleen, testes, and thymus of rats, which had been fed a commercial rat diet containing 03 mg Se/kg diet In the plasma, the erythrocytes, and the soluble fraction of the tissues (with the exception of femur and hair) the activity of the glutathione peroxidase (GSH-Px) was measured, using both hydrogen peroxide and t-butyl hydroperoxide as substrates From the masses of the tissues and the values for the selenium content and the GSH-Px activity, the distribution of the element and the enzyme in the body was calculated For selenium the main pools were the muscle and the liver, and for the GSH-Px, the liver and the erythrocytes By comparing the selenium content and the GSH-Px activity the percentage of the tissue selenium, which was bound to the enzyme in the soluble tissue fraction, was estimated This percentage differed considerably from tissue to tissue, the highest value being found in the erythrocytes and the smallest in the testes According to this estimation the majority of the selenium in the rat is not contained in the GSH-Px but in other compounds

Walter Wolters

Papers

Distribution of selenium and glutathione peroxidase in the rat.