Georg Waeg

University of Graz

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Neven Žarković

Institute of Orthopedics Banjica

KŽ

Kamelija Žarković

University of Zagreb

AČ

Ana Čipak Gašparović

Rudjer Boskovic Institute

Morana Jaganjac

Rudjer Boskovic Institute

Hermann Esterbauer

University of Graz

Suzana Borović

Rudjer Boskovic Institute

Franz Tatzber

Medical University of Graz

Lidija Milković

Rudjer Boskovic Institute

Herbert Puhl

University of Graz

Iva Lončarić

University Hospital Centre Zagreb

Cooperative Institutions

University of Graz

University of Zagreb

Rudjer Boskovic Institute

University Hospital Centre Zagreb

Medical University of Graz

University of Kentucky

Medical University of Białystok

Inserm

University of Osijek

University Hospital Dubrava

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Influence of spleen cells on the growth of liver cells exposed to oxidative stress in vitro

Suzana Borović Ana Čipak Gašparović Kamelija Žarković Tea Kališnik Senka Sabolović

Previous studies evaluated the influence of mitogens, partial hepatectomy and other factors on liver regeneration. Oxidative stress was also investigated as well as its influence on development of tumors and degenerative processes on liver, lungs and arteries. The main aim of the study was to investigate interactions between spleen and liver cells in condition of oxidative stress induced by HNE. Results have shown that in physiological (1?M) concentration, HNE is cell growth modulator, but the liver cell growth is inhibited by high, cytotoxic concentration of HNE (100?M). The spleen cells also inhibit liver cell growth, but only if present in relatively high proportion to liver cells (1:40). Liver cells damaged by cytotoxic concentration of HNE (verified by the specific immunocytochemical determination of the HNE-protein conjugates in the cells) can recover with the help of spleen cells, therfore, it seems likely that spleen cells do not only eliminate damaged cells during liver regeneration, but also assist their recovery if the damage was associated with the lipid peroxidation. So, HNE is important factor of systemic control of the growth of liver cells, as a growth facter and as modifier of the immune response (involving spleen cells) to the liver damage and consequential regeneration, i.e. proliferation of the liver cells.

Liver Regeneration

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

European Journal of Pharmacology (2006)

Suzana Borović Г. Тирзитис Dace Tirzīte Ana Čipak Gašparović Gholam Ali Khoschsorur

Trolox

ABTS

Viability assay

10.1016/j.ejphar.2006.03.004

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Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Cells (2022)

Neven Žarković Antonia Jakovčević Ana Mataić Morana Jaganjac Tea Vuković

A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs). All the immunohistochemical slides were simultaneously prepared for each analyzed biomarker. The results revealed abundant 4-HNE in the vital organs, but the primary origin of 4-HNE was sepsis-like vascular stress, not an oxidative burst of the inflammatory cells. In particular, inflammatory cells were often negative for 4-HNE, while blood vessels were always very strongly immunopositive, as was edematous tissue even in the absence of inflammatory cells. The most affected organs were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytes, whereas despite acute tubular necrosis, 4-HNE was not abundant in the kidneys, which had prominent SOD2. Although SOD2 in most cases gave strong immunohistochemical positivity similar to 4-HNE, unlike 4-HNE, it was always limited to the cells, as was MPO. Due to their differential expressions in blood vessels, inflammatory cells, and the kidneys, we think that SOD2 could, together with 4-HNE, be a potential link between a malfunctioning immune system, oxidative stress, and vascular stress in lethal COVID-19.

SOD2

4-Hydroxynonenal

10.3390/cells11030444

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4-Hydroxynonenal in Human and Animal Chronic Liver Diseases

Acta Clinica Croatica (2009)

Marijana Ćorić Željko Grabarević Marina Štroser Luka Andrišić Georg Waeg

The aldehyde 4-hydroxynonenal (HNE), peroxidation product of polyunsaturated fatty acids is considered the most reliable indicator of endogenous lipid peroxidation in vivo (1). Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. Oxidative stress is epiphenomenon of hepatitis and pathogenic factor of liver cirrhosis, while HNE acts as growth regulating factor and signaling molecules (2). The aim of present study was to investigate the presence of HNE-modified proteins in human and in animal cirrhotic liver by immunohistochemistry. 30 fixed paraffin-embedded liver samples with cirrhosis were retrospectively selected for the study. There were 4 cases of cardiac liver cirrhosis in dogs, and 30 cases of various human chronic liver diseases in stage of cirrhosis. There were 15 cases of chronic hepatitis C and B, 4 cases of hemochromatosis, 4 cases of Wilson's disease and 3 cases of alcoholic cirrhosis. Slides of paraffin-embedded tumor tissue were prepared for immunohistochemistry with monoclonal antibodies to HNE-histidine conjugate. Positive immunohistochemical reaction to HNE was analyzed semi-quantitatively. Intracellular HNE adduct localized in the cytoplasm of hepatocytes was detected respectively in 25 of 30 cases (83%).The strongest staining was noticed in cases of Wilson’s disease, hemochromatosis, alcoholic liver diseases and cardiac liver cirrhosis in dogs. Weak staining was observed in cases of chronic hepatitis C and B. The results of the study indicate that HNE can be detected in several chronic human and in animal liver diseases. Therefore, detection of lipid peroxidation could be used in predicting development of fibrosis and cirrhosis in chronic liver diseases.

4-Hydroxynonenal

Steatohepatitis

Liver disease

Alcoholic Hepatitis

Chronic liver disease

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Lipid peroxidation end product as a modulator of cell growth

Suzana Borović Šunjić Renate Wildburger Martin Mittelbach Georg Waeg Neven Žarković

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Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies

Redox Biology (2017)

Nevenka Piskač Živković Mladen Petrovečki Čedna Tomasović Lončarić Igor Nikolić Georg Waeg

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue.Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts.Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors.Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer.

4-Hydroxynonenal

10.1016/j.redox.2017.01.005

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Citations (26)

Biochemical structural and functional properties of oxidized low-density lipoprotein

Chemical Research in Toxicology (1990)

Hermann Esterbauer Martina Dieber‐Rotheneder Georg Waeg G Striegl Guenther Juergens

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiochemical structural and functional properties of oxidized low-density lipoproteinHermann Esterbauer, Martina Dieber-Rotheneder, Georg Waeg, Georg Striegl, and Guenther JuergensCite this: Chem. Res. Toxicol. 1990, 3, 2, 77–92Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/tx00014a001https://doi.org/10.1021/tx00014a001research-articleACS PublicationsRequest reuse permissionsArticle Views514Altmetric-Citations430LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

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10.1021/tx00014a001

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Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer

Free Radical Biology and Medicine (2016)

Huiqin Zhong Mengqing Xiao Kamelija Žarković Mingjiang Zhu Rina Sa

10.1016/j.freeradbiomed.2016.10.494

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Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder

Biomolecules (2021)

Matea Nikolac Perković Lidija Milković Suzana Uzun Ninoslav Mimica Nela Pivac

Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD.

4-Hydroxynonenal

Protein Carbonylation

10.3390/biom11091365

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

Acta Biochimica Polonica (2010)

Lidija Mrakovčić Renate Wildburger Morana Jaganjac Marina Cindrić Ana Čipak Gašparović

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. We found that HNE generated in bone cells grown in vitro on the surfaces of bioactive glasses 45S5 and 13-93. This raises an interesting possibility of combined action of HNE and ionic bioglass dissolution products in enhanced osteogenesis probably through a mitogen-activated protein kinase (MAPK) pathway. While the proposed mechanism still has to be elucidated, the finding of HNE generation on bioglass offers a new interpretation of the osteoinducting mechanisms of bioglass and suggests the possibility of tissue engineering based on manipulations of oxidative homeostasis.

4-Hydroxynonenal

Homeostasis

Bioactive Glass

10.18388/abp.2010_2391

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Citations (19)