"Alphabet" Selenoproteins: Their Characteristics and Physiological Roles.

Selenium (Se) is a metalloid that is recognized as one of the vital trace elements in our body and plays multiple biological roles, largely mediated by proteins containing selenium-selenoproteins. Selenoproteins mainly have oxidoreductase functions but are also involved in many different molecular signaling pathways, physiological roles, and complex pathogenic processes (including, for example, teratogenesis, neurodegenerative, immuno-inflammatory, and obesity development). All of the selenoproteins contain one selenocysteine (Sec) residue, with only one notable exception, the selenoprotein P (SELENOP), which has 10 Sec residues. Although these mechanisms have been studied intensely and in detail, the characteristics and functions of many selenoproteins remain unknown. This review is dedicated to the recent data describing the identity and the functions of several selenoproteins that are less known than glutathione peroxidases (Gpxs), iodothyronine deiodinases (DIO), thioredoxin reductases (TRxRs), and methionine sulfoxide reductases (Msrs) and which are named after alphabetical letters (i.e., F, H, I, K, M, N, O, P, R, S, T, V, W). These "alphabet" selenoproteins are involved in a wide range of physiological and pathogenetic processes such as antioxidant defense, anti-inflammation, anti-apoptosis, regulation of immune response, regulation of oxidative stress, endoplasmic reticulum (ER) stress, immune and inflammatory response, and toxin antagonism. In selenium deficiency, the "alphabet" selenoproteins are affected hierarchically, both with respect to the particular selenoprotein and the tissue of expression, as the brain or endocrine glands are hardly affected by Se deficiency due to their equipment with LRP2 or LRP8.

"Alphabet" Selenoproteins: Implications in Pathology.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis depends on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, and detoxification agents for heavy metals, other xenobiotics, and key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity, or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on the one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, and neurodegenerative diseases. This review focuses on the specific roles of selenoproteins named after letters of the alphabet in medicine, which are less known than the rest, regarding their implications in the pathological processes of several prevalent diseases and disease prevention.

Phytomedicine in Joint Disorders.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.

Estimating the yin-yang nature of Western herbs: a potential tool based on antioxidation-oxidation theory.

BACKGROUND: One of the biggest obstacles to progress in traditional Chinese medicine (TCM) development in Western countries is the difficulty of applying the traditional concepts to the Western medicinal plants, which are not traditionally described in ancient literature. During recent years, new advances in the field of understanding Yin/Yang aspects from a modern bioscientific point of view have led to the conclusion that antioxidationoxidation concepts might mirror a Yin-Yang relationship. METHODS: This study was intended to integrate the Yin-Yang theory of the traditional Chinese medicine with modern antioxidation-oxidation theory, and to propose a biochemical tool based on redox parameters (e.g. antioxidant capacity, chemiluminescence-CL signal inducing capacity), usable for the classification of Western medicinal plants from Yin/Yang perspective. Trolox equivalent antioxidant capacity (TEAC) of six vegetal aqueous extracts (Symphitum officinalae (radix)-SYM, Inula helenium (radix)-INU, Calendula officinalis (flores)-CAL, Angelica arhanghelica (folium)ANG(F), Angelica arhanghelica (radix)-ANG(R), Ecbalium Elaterium (fruits)-ECB) and luminol-enhanced chemiluminescence of PMNL on addition of these vegetal extracts were measured. Percentages from the maximal or minimal values obtained were calculated for each extract (TEAC%, PMNL stimulation%, PMNL inhibition%, relative speed of action% (RSA%%)), specific Yin-Yang significance was assigned to each relative parameter. In the end, an integration of all the relative values was done, in order to find a global "Yin" or a "Yang" trait of each vegetal extract. RESULTS: TEAC decreased in the following order: SYM > INU > CAL >ANG(F) > ANG(R > ECB. Three vegetal extracts (SYM > INU > ECB) decreased the luminol-enhanced chemiluminescence of PMNL, two (ANG(R) > ANG(F)) increased it, while one (CAL) had a dual effect. After the integration of the percentages, CAL was found to have a global "Yang" trait, while the rest of the plants had a global "Yin" trait. CONCLUSIONS: TEAC% and PMNL inhibition% appears to correlate with the Yin properties of herbs, while PMNL stimulation% and RSA% might correlate with Yang aspects within the formal TCM classification system, and may be useful criteria in describing the Western herbs from a TCM point of view.

Erythrocyte caspase-3 and antioxidant defense is activated in red blood cells and plasma of type 2 diabetes patients at first clinical onset.

OBJECTIVES: We studied erythrocyte (RBC) caspase-3 activity and oxidative status in plasma and RBCs of 33 patients with type 2 diabetes at first clinical onset and 23 age-matched non-diabetes control subjects. METHODS: Caspase-3 activity was assayed during the life span of RBCs; lipid peroxides and total antioxidant capacity (TEAC) were assessed in plasma and RBCs as indicators of oxidative stress and non-enzymatic antioxidant defense; and superoxide dismutase, catalase, and glutathione peroxidase activity were measured in RBCs as enzymatic antioxidants. RESULTS: We found that, compared to controls, RBCs caspase-3 is activated early in type 2 diabetes (P < 0.05); TEAC and malondialdehyde increased in plasma of patients with early diabetes, even when hypertension and macroangiopathy were present (P < 0.01); and RBCs TEAC, malondialdehyde (P < 0.01), superoxide dismutase, and glutathione peroxidase (P < 0.05) exhibited similar behavior in patients with diabetes and hypertensive patients with diabetes. DISCUSSION: Increased antioxidant defense in plasma and RBCs of early type 2 diabetes patients is a potential mechanism that can overcome oxidative damage induced by reactive oxygen species overproduction, and occurs even in RBCs with a decreased life span. This observation could provide a possible explanation for the controversial effects of antioxidant supplementation in diabetes patients.

Influence of chronic administration of anabolic androgenic steroids and taurine on haemostasis profile in rats: a thrombelastographic study.

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with thrombogenic potential in high doses and long-term administration. Taurine, a widely distributed amino-sulfonic acid, is known for its beneficial effects in hypercoagulable states. In order to assess the impact of chronic administration of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar rats were divided into four equal groups: control group (group C) - no treatment; androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate (DECA); taurine (group T) - received oral supplementation of 2% taurine in drinking water; androgen and taurine group (group AT) - concomitant administration of DECA and taurine. After 12 weeks, blood samples were collected and haemostasis parameters were assessed with the thrombelastographic (TEG) analysis system: reaction time, clot kinetics (K, α), final clot strength, coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased reaction time in group A compared with control (P<0.001), whereas taurine significantly increase reaction time (P=0.01), and this effect was maintained in group AT compared with group A (P=0.009). Similar differences between groups have been recorded for the clot kinetics parameters K, α. The final clot strength and coagulation index were significantly increased in group A versus group C (P=0.04, respectively P<0.001), but not in group AT versus group C (P>0.05). There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an accelerated clot development and an increased clot firmness in Wistar rats. Taurine association ensures a protective effect against this hypercoagulable state, partially restoring the altered parameters of the coagulation profile.

A new insight into estrogen signaling: Yin-Yang perspective.

During recent years, new advances in the field of estrogen signaling (e.g., the discovery of the second estrogen receptor named ERß) have led to the conclusion that all the major human tissues are estrogen-responsive. The impact of estrogen on human health is far more complex and stronger than scientists had previously thought. Several scientists suggested that the interplay between ERα and ERß (antagonism, synergism, etc.) simulates a Yin-Yang relationship. This article is intended to integrate the Yin-Yang theory of Traditional Chinese Medicine with modern scientific findings on estrogen signaling to offer a better understanding of the complex interactions between ERα and ERß. A different approach, such as that of Yin-Yang theory, may complete the standard scientific perspective, reveal hidden meanings of the tissue-dependent ERα-ERß predominance, and reveal new aspects of estrogen-receptor imbalance.

Chelidonium majus--an integrative review: traditional knowledge versus modern findings.

Chelidonium majus L. (family Papaveraceae), or greater celandine, is an important plant in western phytotherapy and in traditional Chinese medicine. Crude extracts of C. majus as well as purified compounds derived from it exhibit a broad spectrum of biological activities (antiinflammatory, antimicrobial, antitumoral, analgesic, hepatoprotective) that support some of the traditional uses of C. majus. However, herbal medicine also claims that this plant has several important properties which have not yet been scientifically studied: C. majus is supposed to have diuretic, antitussive and eye-regenerative effects. On the other hand, C. majus also has scientifically proven effects, e.g. anti-osteoporotic activity and radioprotection, which are not mentioned in traditional sources. Moreover, recent controversy about the hepatoprotective versus hepatotoxic effects of Chelidonium majus has renewed the interest of the medical community in this plant. This review is intended to integrate traditional ethno-medical knowledge and modern scientific findings about C. majus in order to promote understanding of its therapeutic actions as well as its toxic potential.

Protection of erythrocyte membrane against oxidative damage by geriforte in healthy human subjects.

The influence of Geriforte, an Ayurvedic natural supplement, on the antioxidant defense systems in human erythrocytes and plasma was investigated in an open human clinical study. The ability of Geriforte to inhibit the azo-bis 2-amidinopropane dihydrochloride (AAPH) dependent lysis of erythrocytes was also evaluated. Geriforte supplementation increased the activity of erythrocyte catalase (265.745 +/- 15.768 vs. 352,329 +/- 18.480 K/g Hb/mL, p < 0.01) and reduced the free radical mediated cytotoxicity induced by azo-bis 2-amidinopropane dihydrochloride (AAPH), which was measured by erythrocyte membrane stability assay (0.0439 +/- 0.0069 vs. 0.1291 +/- 0.0396 C50- AAPH (mM), p < 0.05). The intervention did not change significantly the activity of erythrocyte superoxide dismutase and the plasma levels of antioxidant agents. The results indicate that Geriforte possesses cytoprotective properties on erythrocytes against oxidative challenge and specific antioxidant activity, which involves mainly the intracellular protective systems and the membranes.

Influence of epoietinum therapy on the oxidative stress in haemodialysis patients.

BACKGROUND: The causes of oxidative stress in haemodialysis (HD) patients are still controversial. Beside the uraemic state and dialysis-related factors, adjuvant drug therapies such as epoietinum (rHuEpo) and intravenous iron were involved. METHODS: Several parameters related to oxidative stress were assessed by spectrophotometry in stable HD patients, treated for at least 2 months with epoietinum (n = 14; mean dose = 97.7 +/- 19.1 U/kg/week) or not (n = 15), none of them on iron therapy, and in 13 controls. Plasma thiobarbituric acid-reactive substances (TBARS) were used as markers of reactive species generation. Erythrocyte and plasma antioxidant systems, reflected by non-protein erythrocyte thiols, and erythrocyte enzyme activities -- superoxide dismutase (SOD), glutathione peroxidase, catalase and plasma total thiols, respectively -- were also investigated. RESULTS: There were no differences between HD subgroups regarding haemoglobin levels. Plasma TBARS was increased in all HD patients as opposed to controls, irrespective of rHuEpo therapy. In addition, no change in antioxidant status parameters between rHuEpo-treated and -untreated patients was observed. Except for SOD, the other antioxidant indices were higher in all HD patients versus controls. CONCLUSIONS: These results suggest that (1) chronic HD patients appear to have simultaneously enhanced reactive species generation and antioxidative systems efficiency, and (2) epoietinum therapy did not change their oxidative status, at least in the absence of concomitant iron supplementation and at similar haemoglobin levels.