Pathophysiology of neutrophil-mediated extracellular redox reactions.

Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword.

Pathophysiological relevance of aldehydic protein modifications.

There is growing body of evidence that oxidative stress, i.e. excess in production of reactive oxygen species, can lead to covalent modification of proteins with bioactive aldehydes that are mostly produced under lipid peroxidation of polyunsaturated fatty acids.

Even stressed cells are individuals: second messengers of free radicals in pathophysiology of cancer.

Pathophysiological processes associated with disturbances in cell and tissue oxidative homeostasis, are associated with self-catalyzed process of lipid peroxidation. The end products of lipid peroxidation are reactive aldehydes such as 4-hydroxy-2-nonenal (HNE), acting as "second messengers of free radicals." Although reactive aldehydes were first recognized only as cytotoxic, new evidence has come to light, related to their cell growth regulatory functions achieved through cell signaling.

Stobadine attenuates impairment of an intestinal barrier model caused by 4-hydroxynonenal.

Alterations in the intestinal barrier permeability occur in a broad spectrum of abdominally related pathologies, mostly due to disturbed oxidative homeostasis and increased lipid peroxidation. 4-Hydroxynonenal (HNE), a major lipid peroxidation product, is physiologically present in healthy gastric mucosa, but is increased in early stages of colon cancer and patients with duodenal peptic ulcer. Nevertheless, such supraphysiological levels of HNE have not yet been associated with increased intestinal permeability, even though, as we have described in this paper, they could play important role.

Endogenous 4-hydroxy-2-nonenal in microalga Chlorella kessleri acts as a bioactive indicator of pollution with common herbicides and growth regulating factor of hormesis.

Oxidative stress, i.e. excessive production of reactive oxygen species (ROS), leads to lipid peroxidation and to formation of reactive aldehydes (e.

Growth modulation of human cells in vitro by mild oxidative stress and 1,4-dihydropyridine derivative antioxidants.

Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation.

Effects of bioreactive acrolein from automotive exhaust gases on human cells in vitro.

Acrolein is a toxic unsaturated aldehyde and widespread environmental pollutant produced during lipid peroxidation and also by burning of tobacco or liquid fuels. Inhalation or dermal exposure to acrolein could be toxic to organisms. This very reactive aldehyde has a strong affinity for binding to proteins thus forming pathogenic protein-adducts.

Reversal of multidrug resistance in murine lymphoma cells by amphiphilic dihydropyridine antioxidant derivative.

Background: Multidrug resistance, the principal mechanism by which cancer cells develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapies.

Aim: The aim of the study was to investigate the effect of K-2-11 on the reversal of multidrug resistance.

Materials And Methods: The effects of amphiphilic dihydropyridine derivative K-2-11 were tested on MDR1-expressing mouse lymphoma cells and their parental control.

Natural and synthetic antioxidants: an updated overview.

Abstract The current understanding of the complex role of ROS in the organism and pathological sequelae of oxidative stress points to the necessity of comprehensive studies of antioxidant reactivities and interactions with cellular constituents. Studies of antioxidants performed within the COST B-35 action has concerned the search for new natural antioxidants, synthesis of new antioxidant compounds and evaluation and elucidation of mechanisms of action of both natural and synthetic antioxidants. Representative studies presented in the review concern antioxidant properties of various kinds of tea, the search for new antioxidants of herbal origin, modification of tocopherols and their use in combination with selenium and properties of two promising groups of synthetic antioxidants: derivatives of stobadine and derivatives of 1,4-dihydropyridine.

Growth suppression of human breast carcinoma stem cells by lipid peroxidation product 4-hydroxy-2-nonenal and hydroxyl radical-modified collagen.

Breast cancer is a leading cause of mortality and morbidity in women, mostly due to high metastatic capacity of mammary carcinoma cells. It has been revealed recently that metastases of breast cancer comprise a fraction of specific stem-like cells, denoted as cancer stem cells (CSCs). Breast CSCs, expressing specific surface markers CD44(+)CD24(-/low)ESA(+) usually disseminate in the bone marrow, being able to spread further and cause late metastases.

Double-edged sword behaviour of gallic acid and its interaction with peroxidases in human microvascular endothelial cell culture (HMEC-1). Antioxidant and pro-oxidant effects.

A previous report from our group had shown in vitro a direct interaction between peroxidases and dietary antioxidants at physiological concentrations, where in the absence of H(2)O(2), the antioxidants could serve as oxidizing substrates for the peroxidases. However, the physiological relevance of those findings had not been evaluated. The main objective of this study was to determine whether the oxidizing products produced in the interaction between peroxidase and gallic acid at a physiological concentration of 1 microM may promote cell death or survival in a human microvascular endothelial cell line (HMEC-1).

Interval hypoxic training in complex treatment of Helicobacter pylori-associated peptic ulcer disease.

This study was aimed to demonstrate the efficacy of interval hypoxic training (IHT) in complex treatment of Helicobacter pylori-associated duodenal peptic ulcer disease (DPUD) by parameters of aerobic metabolism and indexes of heart rate variability (HRV). Eighty patients with H. pylori-associated DPUD were included into the study, mean age 32+/-1.

Lipid peroxidation product 4-hydroxynonenal as factor of oxidative homeostasis supporting bone regeneration with bioactive glasses.

Bone regeneration is a process of vital importance since fractures of long bones and large joints have a highly deleterious impact on both, individuals and society. Numerous attempts have been undertaken to alleviate this severe medical and social problem by development of novel bioactive materials, among which bioactive glass is the most attractive because of its osteoconductive and osteostimulative properties. Since lipid peroxidation is an important component of systematic stress response in patients with traumatic brain injuries and bone fractures, studies have been undertaken of the molecular mechanisms of the involvement of 4-hydroxynonenal (HNE), an end product of lipid peroxidation, in cellular growth regulation.

Induction of CMV-1 promoter by 4-hydroxy-2-nonenal in human embryonic kidney cells.

Oxidative stress, i.e., excessive production of oxygen free radicals and reactive oxygen species, leads to lipid peroxidation and to formation of reactive aldehydes which act as second messengers of free radicals.

Influence of 4-hydroxynonenal and spleen cells on primary hepatocyte culture and a novel liver-derived cell line resembling hepatocyte stem cells.

Liver is a unique mammalian organ with a great capacity of regeneration related to its function. After surgical resection or injury, hepatic cells, especially hepatocytes, can proliferate rapidly to repair the damage and to regenerate the structure without affecting the function of the liver. Loss of catalase activity during regeneration indicates that oxidative stress is present in the liver not only in pathological conditions but also as a 'physiological' factor during regeneration.

Ergometry induces systemic oxidative stress in healthy human subjects.

Oxidative stress is an important pathogenic factor of cancer and cardiovascular, metabolic and degenerative diseases. On the other hand, mild oxidative stress, as in case of physical exercise, can increase the antioxidant defense system. However, the mechanisms underlying such desirable effects of mild oxidative stress are not well understood, because the production of hydroxyl radical, the most aggressive oxygen free radical, was not yet evaluated under physiological circumstances.

Distribution of 4-hydroxynonenal-protein conjugates as a marker of lipid peroxidation and parameter of malignancy in astrocytic and ependymal tumors of the brain.

Aims And Background: Lipid peroxidation (LPO) is an autocatalytic process caused by oxidative stress. It results in the production of 4-hydroxynonenal (HNE), which plays a crucial role in hypoxic brain injury, neuronal degeneration and apoptosis. The aim of this study was to evaluate the expression of HNE in 120 astrocytic and 40 ependymal tumors in relation to tumor type, grade of malignancy, angiogenesis, and presence of necrosis and apoptosis.

Lipid peroxidation product acrolein as a predictive biomarker of prostate carcinoma relapse after radical surgery.

Cancer recurrence after radical surgery might happen even in the case of patients with localized prostate carcinoma treated by radical prostatectomy. Therefore, identifying predictive markers of tumour recurrence is very important, so this study evaluated the presence of lipid peroxidation product acrolein in primary prostate carcinomas, assuming that acrolein could be involved in prostate carcinogenesis as was recently shown for colon cancer. Samples obtained by radical prostatectomy of 70 patients were analysed, out of which 27 patients suffered afterwards from tumour recurrence, while 43 patients were disease free.

HNE-protein adducts formation in different pre-carcinogenic stages of hepatitis in LEC rats.

Lipid peroxidation is highly associated with chronic degenerative diseases such as cancer. 4-hydroxy-2-nonenal is one of the major products of lipid peroxidation. 4-hydroxy-2-nonenal can interact with biomolecules, changing their conformation and activity.

Oxidative stress in small-for-gestational age (SGA) term newborns and their mothers.

This study used malondialdehyde (MDA) determination by HPLC and enzymatic assays for total serum peroxides and antioxidant capacity to evaluate oxidative stress in 47 healthy full-term small-for-gestational age (SGA) newborns vs 67 appropriate-for-gestational age (AGA) newborns. Blood samples were collected at delivery from umbilical cord artery and vein and from peripheral blood of the babies on the third day after birth. Blood samples of mothers were also collected and compared with blood of 29 normal non-pregnant women (NPW).

Adaptation to oxidative stress induced by polyunsaturated fatty acids in yeast.

To create a conditional system for molecular analysis of effects of polyunsaturated fatty acids (PUFA) on cellular physiology, we have constructed a strain of yeast (Saccharomyces cerevisiae) that functionally expresses, under defined conditions, the Delta12 desaturase gene from the tropical rubber tree, Hevea brasiliensis. This strain produces up to 15% PUFA, exclusively under inducing conditions resulting in production of 4-hydroxy-2-nonenal, one of the major end products of n-6 polyunsaturated fatty acid peroxidation. The PUFA-producing yeast was initially more sensitive to oxidative stress than the wild-type strain.

Differential sensitivity to 4-hydroxynonenal for normal and malignant mesenchymal cells.

Normal and malignant cells of various origin differ in their sensitivity to oxidative stress. Therefore, we used normal and malignant mesenchymal cells--human osteosarcoma cells (HOS and 143B), human fibroblasts (WI38) and two primary cultures of normal human osteoblasts to test sensitivity to reactive aldehyde 4-hydroxynonenal (HNE), known as a second messenger of free radicals and a signaling molecule. Upon HNE-treatment, decrease in cell viability (by Trypan-blue), apoptosis induction (by TiterTACS TUNEL assay), HNE-protein binding (by HNE-His ELISA) were higher in malignant than in normal cells, while glutathione content was higher in normal cells.

Bioactive 1,4-dihydroisonicotinic acid derivatives prevent oxidative damage of liver cells.

1,4-Dihydroisonicotinic acid derivatives (1,4-DHINA) are compounds closely related to derivatives of 1,4-dihydropyridine, a well-known calcium channel antagonists. 1,4-DHINA we used were derived from a well-known antioxidant Diludin. Although some compounds have neuromodulatory or antimutagenic properties, their activity mechanisms are not well known.

Saccharomyces cerevisiae strain expressing a plant fatty acid desaturase produces polyunsaturated fatty acids and is susceptible to oxidative stress induced by lipid peroxidation.

Although oxygen is essential for aerobic organisms, it also forms potentially harmful reactive oxygen species. For its simplicity, easy manipulation, and cultivation conditions, yeast is used as an attractive model in oxidative stress research. However, lack of polyunsaturated fatty acids in yeast membranes makes yeast unsuitable for research in the field of lipid peroxidation.

The influence of 4-hydroxy-2-nonenal on proliferation, differentiation and apoptosis of human osteosarcoma cells.

The product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE) is known to cause cell death at high concentrations, while at lower concentrations it can influence cell proliferation and differentiation. In our experiments we used human osteosarcoma cells (HOS), to test the influence of HNE on cell proliferation, differentiation and induction of apoptosis. Apoptosis induction was estimated by TiterTACS TUNEL test.