Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research.

Ochratoxin A (OTA) is considered as the most toxic of the other ochratoxins synthesized by various fungal species belonging to the Aspergillus and Penicillium families. OTA commonly contaminates food and beverages, resulting in animal and human health issues. The toxicity of OTA is known to cause liver damage and is still being researched. However, current findings do not provide clear insights into the toxin mechanism of action. The current studies focusing on the use of potentially protective compounds against the effects of the toxin are insufficient as they are mainly conducted on animals. Further research is required to fill the existing gaps in both fields (namely the exact OTA molecular mechanism and the prevention of its toxicity in the human liver). This review article is a summary of the so far obtained results of studies focusing on the OTA hepatotoxicity, its mode of action, and the known approaches of liver cells protection, which may be the base for expanding other research in near future.

Fungal polysaccharides represent a structurally diverse group of bioactive compounds with increasing recognition for their hepatoprotective potential. This review synthesizes current evidence on their roles in the prevention and treatment of liver diseases, including alcohol-related liver disease (ALD), metabolic dysfunction-associated fatty liver disease (MAFLD), or toxin-induced injury. The analyzed studies demonstrate that polysaccharides isolated from species such as Lentinula edodes, Grifola frondosa, Ganoderma lucidum, Coriolus versicolor, and Cordyceps militaris exert beneficial effects by reducing oxidative stress, attenuating inflammation, and improving metabolic homeostasis. Mechanistically, these effects are mediated through the regulation of multiple signaling pathways, including Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Nuclear factor erythroid 2–related factor 2 (Nrf2), and NOD-like receptor protein 3 (NLRP3) inflammasome, as well as modulation of gut microbiota. Fungal polysaccharides were also shown to improve hepatic function by lowering serum biomarkers of liver injury and ameliorating histopathological damage. Presented evidence indicates that fungal polysaccharides possess considerable potential as multifunctional hepatoprotective agents, highlighting the need for further mechanistic insight and clinical validation.

Ochratoxin A (OTA) is a widespread foodborne mycotoxin that poses significant risks to both human and animal health. Upon ingestion, the gastrointestinal tract (GIT) becomes the main site of exposure, where OTA interacts directly with the intestinal epithelium and resident microbiota. Research indicates that OTA disrupts the integrity of the intestinal barrier and alters its permeability. Moreover, OTA undergoes transport and partial metabolism within the intestine before being excreted. Detoxification pathways for OTA include enzymatic degradation and adsorption by microorganisms. Notably, OTA has profound toxic effects on the gut ecosystem; it can alter the relative abundance of bacterial taxa by reducing beneficial populations and promoting opportunistic or pathogenic strains. These changes contribute to an imbalance in the microbiota, impairing host metabolic and immune functions. This dysbiosis is characterized by disrupted microbial homeostasis and impaired communication between the host and its gut microbiome. This review highlights the dual role of the intestine as both a target and a modulator of OTA toxicity. It emphasizes the importance of gut microbiota in mediating the toxicological outcomes of OTA and explores microbiome-based strategies as potential avenues for detoxification.

Ochratoxin A (OTA) is a widespread mycotoxin with documented nephrotoxic, hepatotoxic, immunotoxic, and carcinogenic effects, while its role in hematological malignancies and immune cells remains insufficiently defined. This study examined the cytotoxic and pro-apoptotic OTA activity in three human leukemia cell lines (CCRF-CEM, K-562, HL-60) and in peripheral blood mononuclear cells (PBMCs) from healthy donors. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue assays, mitochondrial membrane potential (ΔΨM) was assessed with JC-1 dye, caspase-3/7 activity was measured by flow cytometry, and the expression of apoptosis-related genes was analyzed by RT-qPCR. OTA did not significantly affect viability, mitochondrial function, or caspase activity in leukemia cell lines, suggesting relative resistance to OTA-induced apoptosis. In contrast, PBMCs exhibited clear dose- and time-dependent sensitivity, manifested by reduced viability, ΔΨM, caspase-3/7 activation, and transcriptional changes consistent with intrinsic apoptosis, including decreased BCL-2 (anti-apoptotic) and increased BAX (pro-apoptotic), APAF1 (apoptosome component), CASP3, and CASP9 (executioner and initiator caspases) expression. These findings demonstrate that OTA selectively targets healthy immune cells rather than leukemia cells, highlighting its pronounced immunotoxic risk and the importance of caution when considering its effect in a hematological context. Although limited to in vitro models, this study underscores the necessity of further research to clarify the molecular basis of differential OTA sensitivity and its contribution to immunosuppression and hematological disease.