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.
Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine.