[Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6) contents in rat heart and brain]. / Wplyw pola magnetycznego niskiej czestotliwosci stosowanego w magnetoterapii na zawartosc interleukiny 6 (IL-6) w sercu i mózgu szczura.

BACKGROUND: The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. MATERIAL AND METHODS: The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. RESULTS: Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). CONCLUSIONS: The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523.

[Influence of ET-1 and ETA receptor blocker (BQ123) on the level of TNF-α in the brain rat]. / Wplyw ET-1 i blokera recetora ETA (BQ123) na zawartosc TNF-alfa w mózgu szczura.

UNLABELLED: Endothelin 1 (ET-1) in addition to the vasoconstriction, also has mitogenic, proinflammatory and proagregation activities. The mediators of inflammatory responses are cytokines, including special role attributed to tumor necrosis factor (TNF-α). AIM: The aim of this study was to evaluate the effect of ET-1 and its receptor blocker (BQ123) on the level of TNF-α in the brain rat. MATERIALS AND METHODS: Experiments were performed on four groups of Wistar-Kyoto rats. Animals were divided into four groups of 8 rats. Group I - control was administered into the tail vein solution of 0.9 % NaCl. Group II - saline followed by ET-1 (3 µg/kg b.w.). Group III - saline followed by BQ123 (1 mg/kg b.w.). Group IV (BQ123/ET-1) - BQ123 (1 mg/kg b.w.) administered 30 min before ET-1 (3 µg/kg b.w.). RESULTS: Administration of ET-1 at doses of 3 µg/kg b.w. resulted in a statistically significant increase in TNF-α concentrations in brain homogenates compared to the control group (p<0.01). Administration of the ET(A) receptor blocker - BQ123 (1mg/kg b.w.) 30 min before administration of ET-1 significantly decreased in TNF-α concentrations in brain homogenates (p <0.01). CONCLUSIONS: ET-1 is significantly increased in TNF-α levels in brain homogenates, while BQ123 given 30 min before administration of ET-1 caused a significant decrease in TNF-α levels, suggesting that its anti-inflammatory activity.

Anti-oxidative and anti-inflammatory effects of lipoic acid in rat liver.

INTRODUCTION: Lipopolysaccharide (LPS) is a key inflammatory component of Gram-negative bacteria, which after entering the systemic circulation contributes to the development of septic hepatic failure. AIM: The aim of this study was to evaluate the effects of alpha lipoic acid (LA) on oxidative stress parameters and inflammation in endotoxemic rat liver. MATERIAL/METHODS: Male Wistar rats were divided into 4 groups, each group consisting of 8 animals. Group I received saline and served as a control, Group II received a single dose of LA (60 mg/kg i.v.), Group III received lipopolysaccharide (LPS) (15 mg/kg i.v.), and Group IV received LPS (15 mg/kg i.v.) and 30 min later received LA (60 mg/kg i.v.). Five hours after LPS or LA administration, the animals were sacrificed and the liver was isolated for measurements of levels of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), total sulfhydryl groups (-SH), total glutathione (tGSH) and reduced glutathione (GSH). RESULTS: Injection of LPS caused a significant increase in liver TBARS and H2O2 levels and a significant decrease in levels of -SH groups, tGSH and GSH. LPS-treated rats also showed an increase in TNF-α and IL-6 levels and edema in the liver. The administration of LA to endotoxemic rats significantly reduced TBARS, H2O2, TNF-α, and IL-6 levels and reduced edema in the liver when compared to the LPS group. This antioxidant also resulted in an increase in -SH groups and tGSH and GSH levels and ameliorated the glutathione redox status when compared to the LPS group. CONCLUSIONS: The results indicated that LA administered 30 min following LPS infusion may effectively prevent oxidative stress and inflammation in the liver. Thus LA is a potent antioxidant that can be useful in rebuilding LPS-induced damaged liver tissue.

[The effects of endothelin 1 and an inhibitor of phosphorylation of IκB on the content of free sulfhydryl groups (-SH) and protein in rat kidney]. / WpLyw endoteliny 1 oraz inhibitora fosforylacji IκB na zawartoSC wolnych grup sulfhydrylowych (-SH) i biaLka w nerce szczura.

UNLABELLED: Endothelin (ET)-1 is a potent vasoconstrictor. ET-1 an increase in the synthesis of transcription factor NF-κB, which is responsible for the production of reactive oxygen species (ROS), and cytokines. AIM: The aim of the study was to determine whether blocking NF-κB pathway affects the content of free -SH groups and total protein in rat kidney homogenates. MATERIALS AND METHODS: Experiments were carried out on four groups of male rats of Wistar-Kyoto strain. Group I - control was administered into the femoral vein solution of 0.9 % NaCl; in group II and III - was given endothelin-1 at doses of 1.5 and 12.5 µg/kg b.w., group IV - was given BAY 11-7082 (inhibitor of phosporylation of IκBα) at a dose of 10 mg/kg b.w. 30 min prior to administration of ET-1 at a dose of 12.5 µg/kg b.w. RESULTS: Administration of ET-1 at doses of 1.5 and 12.5 µg/kg b.w. resulted in a statistically significant reduction of free -SH groups and protein in kidney homogenates compared to the control group. In contrast, administration of an inhibitor of nuclear factor NF-κB (BAY 11-7082 (10 mg/kg b.w.) during the oxidative stress induced by ET-1 (12.5 µg/kg b.w.) significantly increased the concentration of free -SH groups (p <0.001) and protein (p <0.01) in the kidney. CONCLUSIONS: ET-1 caused dose-dependent significant reduction of concentration free -SH groups and total protein. A inhibitor of phosphorylation of IκBα (BAY 11-7082) given during the oxidative stress induced by ET-1 (12.5 µg/kg b.w.) significantly increased the concentration of free -SH groups and protein in the kidney tissue.

[Influence of lipoic acid on the level of TNF-alpha in spleen homogenates]. / Wplyw kwasu liponowego na zawartosc TNF-alpha w homogenatach sledziony.

UNLABELLED: Lipoic acid (LA) is a natural antioxidant and possess beneficial effects on oxidative stress parameters in various tissues. The aim of the study was to estimate of influence of LA on free -SH groups and TNF-alpha levels in spleen homogenates in rats during oxidative stress induced by LPS. MATERIAL AND METHODS: Experiments were performed on Wistar rats devided into 4 groups: group I (control) received 0,9% NaCl; group II --received LA (100 mg/kg); group III received LPS (10 mg/kg); group IV--received LPS (10 mg/kg) and 30 min later received LA at the dose 100 mg/kg. RESULTS: Administration of LA after LPS-induced oxidative stress resulted in statistically significant increase in the level of -SH groups and decrease in the level of TNF-alpha when compared to the LPS group (p < 0.001). CONCLUSION: The early administration of LA after LPS challenge a significant suppressed symptoms of oxidative stress and inflammatory effects LPS, expressed as a increase in -SH groups and decrease in TNF-alpha in the spleen homogenates.

Antioxidant and Anti-inflammatory Effects of α-Lipoic Acid on Lipopolysaccharide-induced Oxidative Stress in Rat Kidney.

α-Lipoic acid (α-LA) is a naturally occurring organosulfur component. Oxidative stress plays an essential role in the pathogenesis of various diseases, such as kidney and cardiovascular diseases, diabetes, neurodegenerative disorders, cancer and aging. Kidneys are especially vulnerable to oxidative stress and damage. The aim of the study was to evaluate the effect of α-LA on lipopolysaccharide (LPS)-induced oxidative stress parameters in rat kidneys. The experimental rats were divided into four groups: I-control (0.9% NaCl i.v.); II-α-LA (60 mg/kg b.w. i.v.); III-LPS (30 mg/kg b.w. i.v.); and IV-LPS + LA (30 mg/kg b.w. i.v. and 60 mg/kg b.w. i.v., respectively). In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), sulfhydryl groups (-SH), total protein, superoxide dismutase (SOD), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulphide (GSSG) and the GSH/GSSG ratio were determined. In addition, the levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-6 were measured to assess inflammation and was estimated kidney oedema. Studies have shown that α-LA administered after LPS administration attenuated kidney oedema and significantly decreased TBARS, H2O2, TNF-α, and IL-6 levels in rat kidneys. α-LA also resulted in increase -SH group, total protein, and SOD levels and ameliorated the GSH redox status when compared to the LPS group. The results suggest that α-LA plays an important role against LPS-induced oxidative stress in kidney tissue as well as downregulating the expression of pro-inflammatory cytokines.

[The influence of endothelin-1 and endothelin receptor blocker on the content of white blood cells in the peripheral blood of rat]. / Wplyw endoteliny-1 i blokera jej receptora A na zawartosc krwinek bialych we krwi obwodowej szczura.

UNLABELLED: The aim of the study was to evaluate the influence of endothelin-1 (ET-1) and endothelin receptor (ETA) blocker (BQ 123) on the content of white blood cells in the peripheral blood of rat. MATERIAL AND METHODS: Experiments were performed on Wistar rats divided into following groups: group I (control) received saline; group II (ET-1) received endothelin-1 (3 microg/kg b.w.); group III (BQ 123) received ETA receptor blocker (1 mg/kg b.w.); group IV (BQ 123+ET-1) received BQ 123 (1 mg/kg b.w) and 30 minutes later ET-1 (3 microg/kg b.w.). Peripheral blood was collected from animals at three time intervals to determine the content of white blood cells using a hematology analyzer MICROS OT 45. RESULTS: Administration of ET-1 resulted in a statistically significant increase in the concentration of white blood cells after 1 hour after administration, compared with the control group. Contrast, administration of a specific blocker of ETA (BQ 123) reduced the leukocyte content after 1 and 5 hours after administration of ET-1. CONCLUSION: Intravenous administration of ET-1 significantly increased the content of white blood cells in peripheral blood of rat via the ETA receptor since reversed its blockage caused the change.

Effect of Alpha-Lipoic Acid on Rat Ventricles and Atria under LPS-Induced Oxidative Stress.

Alpha-lipoic acid (α-LA) is a disulfide compound and one of the most effective antioxidants. Many studies have indicated positive effects of α-LA in the prevention of pathologic conditions mediated by oxidative stress, such as cardiovascular diseases. However, the therapeutic potential of α-LA for the heart has not been explored with regards to the ventricles and atria. The aim of our study was to evaluate the effects of α-LA on oxidative stress parameters and inflammation in the ventricles and atria of the heart in rats under LPS-induced oxidative stress. Wistar rats were divided into 4 groups: I-control (received 2 doses of 0.2 mL of 0.9% NaCl i.v., 0.5 h apart); II-α-LA (received 0.2 mL of 0.9% NaCl and 0.5 h later received α-LA 60 mg/kg b.w. i.v.); III-lipopolysaccharide (LPS) (received 0.2 mL of 0.9% NaCl and 0.5 h later received LPS 30 mg/kg b.w. i.v.); and IV-LPS + LA (received LPS 30 mg/kg b.w. i.v. and 0.5 h later received α-LA 60 mg/kg b.w. i.v.). Five hours later, the rats were euthanized. The hearts were surgically removed and weighed to estimate heart edema. The ventricular and atrium tissue was isolated to measure levels of TNF-α, IL-6, superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), total sulfhydryl groups (-SH), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulfide (GSSG), and the GSH/GSSG ratio. LPS significantly increased TNF-α, IL-6, TBARS, and H2O2 levels and decreased SOD, -SH groups, tGSH, the GSH/GSSG ratio, and GSH levels in rat ventricles and atria while α-LA administered after the injection of LPS significantly decreased TNF-α, IL-6, TBARS, and H2O2 levels. α-LA also increased SOD and -SH group levels and ameliorated the glutathione redox status when compared to the LPS group. Our data suggest that α-LA administration 30 min after LPS infusion may effectively prevent inflammation and oxidative stress in the ventricles and atria.

[Role of lipoic acid in health and disease]. / Rola kwasu liponowego w zdrowiu i chorobie.

Oxidative stress disturbs organism's homeostasis and leads to excessive reactive oxygen species (ROS) production. Researchers are still focused on antioxidants that help to reduce oxidative stress level and are helpful in treatment of diseases were ROS overproduction is observed. Among those antioxidants is lipoic acid (LA). When applied systemically LA accumulates in tissues and is converted to dihyrolipoic acid (DHLA) by lipoamide dehydrogenase. Both LA and DHLA are biologically active. LA scavenges hydroxyl radical, subchloric acid and singlet oxygen. Moreover, LA is able to chelate transient ions. Therefore, LA is used in diabetic nephropaties, fungi or heavy metal intoxication, liver diseases, neurodegenerative and cardiovascular diseases. This review surveys the antioxidant ability of LA and its role in pathological states where increased concentration of ROS is observed.

[Influence of low frequency magnetic field on chosen parameters of oxidative stress in rat's muscles]. / Wplyw pola magnetycznego niskiej czestotliwosci na wybrane parametry stresu oksydacyjnego w tkance miesniowej szczura.

UNLABELLED: Free radicals are atoms, molecules or their fragments, which excess leads to the development of the oxidative stress, which is caused of many neoplasmic, neurodegenerative, inflammatory diseases and aging the organism. The main of exogenous sources of free radicals are among others: industrial pollution, tobacco smoke, ionizing radiation, ultrasound and magnetic field. The low magnetic field is applied in the physician therapy. The aim of this study was to evaluate the influence of low magnetic field on the parameters of oxidative stress in rat's muscles. MATERIALS AND METHODS: Thirty male rats, weight of 280-300 g were randomly divided into three experimental groups: control I and treatment II and III (ELFMF-exposed), each containing seven animals. Animals in treat group II were exposed to 40 Hz, 7 mT for 0.5 h/day for 14 days (this kind of the ELFMF is mostly use in magnetotherapy) while, group III was exposed to 40 Hz, 7 mT for 1 h/day for 14 days. Control rats were in separate room without exposing to ELFMF. Immediately after the last exposure, the part of muscles was taken under pentobarbital anaesthesia. The effects of exposure to ELFMF on oxidative states were assessed on the measurements of concentration of -SH group, H2O2, and the concentration of proteins in muscles homogenates. RESULTS: Exposure to ELFMF: 40 Hz, 7 mT, 30 and 60 min/day used for 2 weeks caused significant increase in -SH group concentration and decrease of the protein concentration in the muscles homogenates. CONCLUSION: Low magnetic field used in magnetotherapy causes the significant changes of the generating the reactive forms of oxygen in the muscles which depend on the parameters of low magnetic field.

Protective effects of early administration of alpha-lipoic acid against lipopolysaccharide-induced plasma lipid peroxidation.

Lipopolysaccharide (LPS), called endotoxin, is a major component of Gram-negative bacteria cell wall. LPS stimulates the synthesis and release of several metabolites from mammalian phagocytes which leads to fulminant systemic inflammation (endotoxic shock). Among LPS-induced metabolites, reactive oxygen species are considered to play crucial role in the pathogenesis of endotoxic shock via oxidative stress generation. In this study, the effect of early administration of antioxidant alpha-lipoic acid (LA) on plasma lipid peroxidation and total antioxidant blood capacity was evaluated in endotoxic shock in rats. Lipid peroxidation was measured as plasma thiobarbituric acid reactive substances (TBARS) levels, while total blood antioxidant capacity was assessed as ferric reducing ability of plasma (FRAP). The endotoxic shock was induced by administration of LPS (Escherichia coli 026:B6, 30 mg/kg, iv) in anesthetized rats. Then, 30 min later, animals were treated intravenously (iv) with LA at 60 mg/kg. After 5 h observation animals were killed and blood from heart was taken for TBARS and FRAP measurements. LPS injected to saline-pretreated animals resulted in development of oxidative stress indicated by significant increases in plasma TBARS and significant decrease in total antioxidant capacity of plasma. Conversely, LA injected to saline pretreated animals caused an increase in FRAP values and the decrease in TBARS levels. The administration of LA 0.5 h after LPS challenge resulted in an increase in FRAP values and decrease in plasma lipid peroxidation as compared to LPS group. Moreover, the levels of TBARS and FRAP in LPS + LA group were similar to those observed in LA group. In conclusion, our present study demonstrates that early treatment with LA significantly protects against endotoxin-induced oxidative stress in rats.

[Estimation of the effect of lipoic acid in the rat's lung during lipopolysaccharide-induced oxidative stress]. / Ocena dzialania kwasu liponowego w plucach szczura w czasie stresu oksydacyjnego wywolanego lipopolisacharydem.

UNLABELLED: The aim of this study was to investigate the effect of lipoic acid (LA) on lipid peroxidation, hydrogen peroxide concentration (H2O2), sulphydryl group (-SH) contents and total capacity protein a few hours after administration lipopolysaccharide (LPS) -induced oxidative stress in rats. MATERIALS AND METODS: Male albino Wistar rats were used in this study. The animals were divided into four groups, each group consisting of ten male animals. Control group received physiological saline alone i.v. The second group was given LA (60 mg/kg b.w., i.v.). The third second group received LPS (30 mg/kg b.w., i.v.). The fourth group received LPS (30 mg/kg b.w., i.v.) and after 0.5h received LA (60 mg/kg b.w., i.v.). In the lung homogenates were measured thiobarbituric acid reactants (TBARS), hydrogen peroxide concentration, -SH groups and protein contents. RESULTS: The administration of LA after to LPS -induced oxidative stress caused a significant decrease in TBARS and H2O2 concentrations (appropriate 3.65 +/- 0.2 microM and 0.014 +/- 0.008 microM) compared with the group treated with LPS (appropriate 6.030 +/- 0.16 microM and 0.189 +/- 0.03 microM). Treatment of LPS-injected rats with LA caused increase in -SH groups and protein concentration (p < 0.05). CONCLUSION: The early administration of LA a significant decreased symptoms of oxidative stress - induced LPS, that shows decrease in lipid peroxidation process, H2O2 concentration and increase in -SH groups and protein contents in rat's lung homogenates.

ET-1 mediates the release of reactive oxygen species and TNF-α in lung tissue by protein kinase C α and ß1.

BACKGROUND: The aim of this study was to determine the involvement of protein kinase C (PKC) in the ET-1 induced generation of reactive oxygen species and TNF-α in rat lungs. METHODS: Experiments were performed on 6 groups of rats: Group I: saline-treated control; Group II: saline followed by endothelin-1 (ET-1) (3µg/kg); Group III: saline followed by selective PKC αß1 inhibitor (Gö6976) (2µg/kg); Group IV: Gö6976 (2µg/kg) administered 30min before ET-1 (3µg/kg); Group V: saline followed by the PKC activator phorbol 12-myristate 13-acetate (PMA) (50µg/kg); Group VI: Gö6976 (2µg/kg) administered 30min before PMA (50µg/kg). After 5h, the animals were euthanized and their lungs were isolated for measurements. RESULTS: ET-1 resulted in increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels and lung edema, as well as a decrease in GSH/GSSG ratio compared to the controls. The level of TNF-α also was elevated in the presence of ET-1. Administration of Gö6976 30min before ET-1 injection significantly decreased lung edema, as well as the concentrations of TBARS, H2O2 and TNF-α, but increased the GSH/GSSG redox ratio compared to ET-1. Conversely, PMA elevated lung edema and TBARS, H2O2 and TNF-α concentrations, but decreased the GSH/GSSG redox ratio compared to the control group. Treatment with Gö6976 significantly ameliorated the PMA-induced oxidative stress parameters, decreased tissue TNF-α level, and lung edema. CONCLUSION: Endothelin-1 induces ROS generation, increases TNF-α level and lung edema via activation of PKC αß1.

The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress.

Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

The role of endothelin-1 and endothelin receptor antagonists in inflammatory response and sepsis.

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor, mainly secreted by endothelial cells. It acts through two types of receptors: ETA and ETB. Apart from a vasoconstrictive action, ET-1 causes fibrosis of the vascular cells and stimulates production of reactive oxygen species. It is claimed that ET-1 induces proinflammatory mechanisms, increasing superoxide anion production and cytokine secretion. A recent study has shown that ET-1 is involved in the activation of transcription factors such as NF-κB and expression of proinflammatory cytokines including TNF-α, IL-1, and IL-6. It has been also indicated that during endotoxaemia, the plasma level of ET-1 is increased in various animal species. Some authors indicate a clear correlation between endothelin plasma level and morbidity/mortality rate in septic patients. These pathological effects of ET-1 may be abrogated at least partly by endothelin receptor blockade. ET-1 receptor antagonists may be useful for prevention of various vascular diseases. This review summarises the current knowledge regarding endothelin receptor antagonists and the role of ET-1 in sepsis and inflammation.

Effects of lipoic acid on spleen oxidative stress after LPS administration.

BACKGROUND: Bacterial endotoxin (lipopolysaccharide - LPS) is a strong modulator of the immune system that plays a crucial role in the pathogenesis of endotoxic shock. The aim of the study was to investigate the effects of lipoic acid (LA) on oxidative stress markers in spleen homogenates obtained from LPS-induced endotoxic shock rats. METHODS: The animals were treated with saline or lipoic acid (LA) (60 or 100 mg/kg b.w. iv) 30 min before or 30 min after LPS administration (30 mg/kg b.w. iv). Five hours after LPS, LA or saline administration, the animals were euthanized and their spleens were isolated for measurements. RESULTS: The LPS-treated animals developed oxidative stress, indicated by a significant increase in thiobarbituric acid-reactive substances (TBARS) and hydrogen peroxide (H2O2) concentrations (p<0.001) as well as an insignificant decrease in the level of sulfhydryl groups (-SH groups) and the glutathione redox ratio [reduced glutathione (GSH) to oxidized glutathione (GSSG) ratio] (p<0.02) as compared with control group. Treatment with LA (60 or 100 mg/kg) before or after LPS administration resulted in an increase in -SH group content (p<0.01) and a decrease in TBARS and H2O2 concentration in the spleen as compared with LPS group (p<0.001). LA (60 or 100 mg/kg) before LPS administration decreased the level of GSSG (p<0.05) and increased the level of GSH in spleen homogenates (p<0.05), resulting in an increase in the GSH/GSSG ratio compared with the LPS group (p<0.01). It also improved the LPS-induced increase in the spleen weight (SW) to body weight (BW) ratio (p<0.001 vs. control). CONCLUSION: The present results have shown that LA is endowed with antioxidant properties that are protective in the spleen against the deleterious actions of Gram-negative bacterial endotoxin.

The NADPH oxidase family and its inhibitors.

The classical nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was originally detected in neutrophils as a multicomponent enzyme that catalyzes the generation of superoxide from oxygen and the reduced form of NADPH. This enzyme is composed of two membrane-bound subunits (p22phox and gp91phox), three cytosolic subunits (p67phox, p47phox, and p40phox) and a small G-protein Rac (Rac1 and Rac2). Recently, it has been demonstrated that there are several isoforms of nonphagocytic NADPH oxidase. Endothelial cells, vascular smooth muscle cells or adventitial fibroblasts possess multiple isoforms of this enzyme. The new homologs, along with gp91phox are now designated the Nox family of NADPH oxidases and are key sources of reactive oxygen species in the vasculature. Reactive oxygen species play a significant role in regulating endothelial function and vascular tone. However, besides the participation in the processes of physiological cell, these enzymes can also be the perpetrator of oxidative stress that causes endothelial dysfunction. This review summarizes the current state of knowledge of the structure and functions of NADPH oxidase and NADPH oxidase inhibitors in the treatment of disorders with endothelial damage.

Lipoic acid - biological activity and therapeutic potential.

α-Lipoic acid (LA; 5-(1,2-dithiolan-3-yl)pentanoic acid) was originally isolated from bovine liver by Reed et al. in 1951. LA was once considered a vitamin. Subsequently, it was found that LA is not a vitamin and is synthesized by plants and animals. LA is covalently bound to the ε-amino group of lysine residues and functions as a cofactor for mitochondrial enzymes by catalyzing the oxidative decarboxylation of pyruvate, α-ketoglutarate and branched-chain α-keto acids. LA and its reduced form - dihydrolipoic acid (DHLA), meet all the criteria for an ideal antioxidant because they can easily quench radicals, can chelate metals, have an amphiphlic character and they do not exhibit any serious side effects. They interact with other antioxidants and can regenerate them. For this reason, LA is called an antioxidant of antioxidants. LA has an influence on the second messenger nuclear factor κB (NF-κB) and attenuates the release of free radicals and cytotoxic cytokines. The therapeutic action of LA is based on its antioxidant properties. Current studies support its use in the ancillary treatment of many diseases, such as diabetes, cardiovascular, neurodegenerative, autoimmune diseases, cancer and AIDS. This review was undertaken to gather the most recent information regarding the therapeutic properties of LA and its possible utility in disease treatment.