Fibrinogen, a pivotal plasma glycoprotein, plays an essential role in hemostasis by serving as the precursor to fibrin, which forms the structural framework of blood clots. Beyond coagulation, fibrinogen influences immune responses, inflammation, and tissue repair. Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and antioxidants, induces fibrinogen oxidation, significantly altering its structure and function. This narrative review synthesizes findings from in vitro, ex vivo, and clinical studies, emphasizing the impact of fibrinogen oxidation on clot formation, architecture, and degradation. Oxidative modifications result in denser fibrin clots with thinner fibers, reduced permeability, and heightened resistance to fibrinolysis. These structural changes exacerbate prothrombotic conditions in cardiovascular diseases, diabetes, chronic inflammatory disorders and cancer. In contrast, “low-dose” oxidative stress may elicit protective adaptations in fibrinogen, preserving its function. The review also highlights discrepancies in experimental findings due to variability in oxidation protocols and patient conditions. Understanding the interplay between oxidation and fibrinogen function could unveil therapeutic strategies targeting oxidative stress. Antioxidant therapies or selective inhibitors of detrimental oxidation hold potential for mitigating thrombotic risks. However, further research is essential to pinpoint specific fibrinogen oxidation sites, clarify their roles in clot dynamics, and bridge the gap between basic research and clinical practice.

Reactive oxygen species (ROS) contribute to endothelial dysfunction, platelet activation, and coagulation abnormalities, promoting thrombus formation. Given the growing interest in non-pharmacological approaches to modulate oxidative stress, we examine the potential of various dietary interventions and antioxidant supplementation in reducing oxidative damage and preventing thrombotic events. Key dietary patterns, such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and ketogenic diets, as well as antioxidant-rich supplements like curcumin, selenium, and polyphenols, demonstrate promising effects in improving oxidative stress markers, lipid profiles, and inflammatory responses. This review highlights recent advances in the field, drawing from in vitro, ex vivo, and clinical studies, and underscores the importance of integrating dietary strategies into preventive and therapeutic approaches for managing thrombosis and cardiovascular health. Further research is needed to better understand long-term effects and personalize these interventions for optimizing patient outcomes.

Cholangiocarcinoma (CCA) is a primary liver tumor that accounts for 2% of all cancer-related deaths worldwide yearly. It can arise from cholangiocytes of biliary tracts, peribiliary glands, and possibly from progenitor cells or even hepatocytes. CCA is characterized by high chemoresistance, aggressiveness, and poor prognosis. Potentially curative surgical therapy is restricted to a small number of patients with early-stage disease (up to 35%). Accumulating evidence indicates that CCA is an oxidative stress-driven carcinoma resulting from chronic inflammation. Oxidative stress, due to enhanced reactive oxygen species (ROS) production and/or decreased antioxidants, has been recently suggested as a key factor in cholangiocyte oncogenesis through gene expression alterations and molecular damage. However, due to different experimental models and conditions, contradictory results regarding oxidative stress in cholangiocarcinoma have been reported. The role of ROS and antioxidants in cancer is controversial due to their context-dependent ability to stimulate tumorigenesis and support cancer cell proliferation or promote cell death. On these bases, the present narrative review is focused on illustrating the role of oxidative stress in cholangiocarcinoma and the main ROS-driven intracellular pathways. Heterogeneous data about antioxidant effects on cancer development are also discussed.

A large proportion of infertile men do not receive a clear diagnosis, being considered as idiopathic or unexplained cases due to infertility diagnosis based on standard semen parameters. Particularly in unexplained cases, the search for new indicators seems mandatory to provide specific information. In the etiopathogenesis of male infertility oxidative stress displays important roles by negatively affecting sperm quality and function. In this study, performed in a population of 34 idiopathic infertile men and in 52 age-matched controls, redox parameters were assessed in blood, leukocytes, spermatozoa, and seminal fluid and related to semen parameters. The main findings indicate that blood oxidative stress markers reflect seminal oxidative stress. Interestingly, blood leukocyte ROS production was significantly correlated to sperm ROS production and to semen parameters. Overall, these results suggest the potential employ of blood redox markers as a relevant and adjunctive tool for sperm quality evaluation aimed to preconception care.

Endometriosis (EM), a chronic inflammatory condition predominantly affecting women of reproductive age, has been linked to an elevated risk of thrombosis, though its underlying molecular mechanisms remain incompletely understood. In this case-control study, involving 71 EM patients and 71 matched controls, we explored the structural and functional changes in fibrinogen and their potential role in thrombosis. Key oxidative stress markers, such as reactive oxygen species (ROS) levels in blood lymphocytes, monocytes, and granulocytes, along with plasma lipid peroxidation markers and total antioxidant capacity, were measured. Fibrinogen structure was examined using circular dichroism spectroscopy and intrinsic fluorescence, while functional properties were evaluated by analyzing thrombin-mediated polymerization and plasmin-induced lysis. Compared to controls, EM patients exhibited elevated ROS production and systemic oxidative stress, leading to notable fibrinogen oxidation and structural alterations. These changes were associated with impaired fibrin polymerization and enhanced resistance to plasmin-induced lysis, which are indicative of a pro-thrombotic state. These findings suggest that oxidative stress-driven fibrinogen modifications may contribute to the heightened thrombotic risk in women with EM, highlighting a potential therapeutic target to mitigate cardiovascular complications.

Homocysteinylation, a post-translational modification involving the covalent attachment of homocysteine to proteins, has emerged as a critical mechanism linking hyperhomocysteinemia to thrombotic disease. This review focuses on the homocysteinylation of fibrinogen, a key coagulation factor, and its impact on clot structure and function. Evidence indicates that elevated homocysteine levels can induce significant changes in fibrin architecture, promoting the formation of dense, rigid clots with reduced permeability and impaired fibrinolytic susceptibility, thus fostering a prothrombotic environment. However, inconsistencies in reported effects on fiber diameter and polymerization kinetics highlight the need for standardized experimental protocols. Advances in proteomics and high-resolution imaging are expected to clarify the molecular underpinnings of these modifications. Moreover, homocysteinylation intersects with oxidative stress and may serve as a mechanistic bridge between metabolic and vascular dysfunction. Understanding its role not only enhances insight into thrombosis but also opens avenues for biomarker discovery and targeted therapies in cardiovascular and potentially neurological disorders.