Food safety organizations indicate the likelihood of constant human and animal exposure to mycotoxin mixtures as a possible negative public health impact. Risk assessment demonstrates that certain mycotoxins of Aspergillus and Penicillium spp. are toxic and hold a significant genotoxic efficacy at nanomolar concentrations. The aim of the current study was to investigate the potential cytogenetic effects of sterigmatocystin (STER), ochratoxin A (OTA) and citrinin (CTN) alone or in combination, at pM to μΜ concentrations, on the human hepatocellular cancer cell line Hep3B. MTT reduction, mitotic divisions, cell cycle delays and sister chromatid exchange rates (SCE) were determined as endpoints of metabolic activity, cytotoxicity, cytostaticity, and genotoxicity, respectively. All mycotoxin treatments induce SCE rates from 10⁻¹² M, while their cytotoxic and cytostatic potential varies. In PRI and MI assays, but not at MTT, STER alone or in combination with OTA + CTN appeared cytostatic and cytotoxic, even at 10⁻¹² M, while CTN alone and all other combinations displayed substantial cellular survival inhibition in doses ≥ 10⁻⁸ M. Co-administration of STER + OTA or STER + CTN in concentrations ≤ 10⁻¹ M, increased the MI and MTT activity, while it did not affect the PRI. Mycotoxin co-treatments revealed in general similar-to-additive or antagonistic genotoxic and cytotoxic effects. Our results for the first time describe that STER alone or in combination with OTA and/or CTN share a cytotoxic and cytogenetic potential even at picoMolar concentrations on human hepatoma cells in vitro.

Background. The aim of this experimental study was to investigate the role of apigenin in liver apoptosis, in an experimental model of hepatic ischemia-reperfusion in rats.Materials and Methods. Forty-eight Wistar rats (apigenin and control groups), 14 to 16 weeks old and weighing 220 to 350 g, were used. They were all subjected to hepatic ischemia by occlusion of the hepatic artery and portal vein for 45 minutes and reperfusion was followed for 60, 120, and 240 minutes. Apigenin was administrated intraperitoneally. Liver tissues were used for the detection of apoptosis by TUNEL assay and caspase 3 antibodies. Expression analysis ofFas/FasLgenes was evaluated by real time PCR.Results. The expression analysis ofFasandFasLgenes was increasing during reperfusion (significantly in the group of 240 minutes of reperfusion). It was in the same group that apigenin decreased Fas receptor levels and inhibited apoptosis as confirmed by TUNEL assay and caspase 3 antibodies.Conclusions. The effects of apigenin in the Fas/FasL mediated pathway of apoptosis, in the hepatic ischemia-reperfusion, seem to have a protective result on the hepatic cell.

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression. Methods: Forty-seven male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD, followed by quercetin treatment for 4 weeks. Mice were divided into baseline, control, and two quercetin groups, receiving low (10 mg/kg) and high (50 mg/kg) doses. Liver histology was scored using the NAFLD Activity Score (NAS). Immunohistochemistry and immunoblotting were performed to analyze autophagy markers. Results: Quercetin-treated groups showed significant reductions in NAS compared to controls (p = 0.011), mainly in steatosis and steatohepatitis. Immunohistochemistry indicated increased expression of autophagy markers LCA and p62 in quercetin groups. Western blot analysis revealed significant elevations in LC3A in the treated groups, suggesting improved autophagic activity and lipid degradation. Conclusions: Quercetin effectively reduces NAFLD severity and modulates autophagy-related proteins. These findings suggest that quercetin enhances autophagic flux, supporting its therapeutic potential for NAFLD. Additional research is needed to clarify the molecular mechanisms of quercetin and to determine the optimal dosing for clinical application.

The inhibitory effect of phenothiazines in tumor growth and cancer cell proliferation in vitro and in vivo has been established. These reports motivated us to investigate the genotoxic, cytotoxic, and cytostatic potential of chlorpromazine, alone or in combination with mitomycin C, in vitro and in vivo. Sister chromatid exchange levels were assessed providing a quantitative index of genotoxicity. In-vitro studies were performed on human lymphocyte cultures and in-vivo studies involved Ehrilch ascites tumor (EAT) cells. An antitumour study was also conducted on the survival time and the ascitic volume in EAT-bearing Balb/C mice. The combination of chlorpromazine plus caffeine and mitomycin C exerted cytostatic and cytotoxic actions in human lymphocytes. The combination of chlorpromazine plus mitomycin C exerted cytostatic and cytotoxic actions in EAT cells, significantly increased the survival span of the mice inoculated with EAT cells, and suppressed the expected tumor growth increase. The findings of this basic study illustrate that high chlorpromazine concentrations increase chemotherapeutic effectiveness of mitomycin C. Chlorpromazine concentrations within the observed human plasma concentration range need to be tested along with antineoplastic agents in vitro for its synergistic action so as to evaluate a potential clinical application. Further investigation including other phenothiazines, biological systems, and cancer models is required.

OBJECTIVE: Modifications in E-cadherin (E-Cad) expression are associated with dedifferentiation, progression, metastases and poor prognosis in many types of tumors. The aim of the present study was to identify a potential association of the pre- and post-operative soluble E-Cad levels (sE-Cad) with the clinicopathological parameters of patients with gastric cancer. PATIENTS AND METHODS: Serum sE-Cad levels were determined in 99 gastric cancer patients and 78 healthy volunteers using ELISA. RESULTS: Levels of sE-Cad were significantly increased in gastric cancer patients compared with these levels in healthy controls (p < 0.001). For the evaluation of the diagnostic significance of sE-Cad the area under the receiver operating characteristic (ROC) curve (AUC) was 0.835, while the optimal cut-off point of 9.9 μg/mL was determined to classify gastric cancer patients, which yielded sensitivity of 72.7%, specificity of 80.8% and accuracy of 76.3%. Poor differentiation (p = 0.009) and the presence of distant metastases (p < 0.001) were the two significant independent prognostic determinants for high sE-Cad levels in multivariate linear regression analysis. The preoperative levels of sE-Cad also proved helpful in classifying patients according to the choice treatment (curative versus palliative) (AUC, 0.656); when the optimal cut-off point was set at 17.60 μg/mL, the sensitivity was 57%, the specificity was 83% and accuracy was 75%. Survival was shorter in patients with increased sE-Cad (median, 7 months vs 39 months, p = 0.0002), although multivariate Cox regression analysis demonstrated a marginal prognostic significance of sE-Cad for survival (adjusted HR = 1.68, 95% CI = 0.93 to 3.02, p = 0.072). CONCLUSIONS: Serum sE-Cad levels could be considered as a diagnostic and prognostic marker in gastric cancer patients as well as a tool to select a treatment approach. The prognostic value of sE-Cad on overall survival requires further study.