Search Results (4)

In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. Full article

The present study addresses the chemoprotective effects of xanthohumol (XN), a prenylated flavonoid found in the female inflorescences (hops) of the plant Humulus lupulus L., against the carcinogenic food contaminant aflatoxin B1 (AFB1). The chemical reactions of XN and its derivatives (isoxanthohumol (IXN), 8-prenylnaringenin (8-PN), and 6-prenylnaringenin (6-PN)) with the AFB1 metabolite, aflatoxin B1 exo-8,9-epoxide (AFBO), were investigated in silico, by calculating activation free energies (ΔG^‡) at the Hartree–Fock level of theory in combination with the 6-311++G(d,p) basis set and two implicit solvation models. The chemoprotective effects of XN were investigated in vitro in the metabolically competent HepG2 cell line, analyzing its influence on AFB1-induced cytotoxicity using the MTS assay, genotoxicity using the comet and γH2AX assays, and cell cycle modulation using flow cytometry. Our results show that the ΔG^‡ required for the reactions of XN and its derivatives with AFBO are comparable to the ΔG^‡ required for the reaction of AFBO with guanine, indicating that XN, IXN, 8-PN, and 6-PN could act as scavengers of AFBO, preventing DNA adduct formation and DNA damage induction. This was also reflected in the results from the in vitro experiments, where a reduction in AFB1-induced cytotoxicity and DNA single-strand and double-strand breaks was observed in cells exposed to combinations of AFB1 and XN, highlighting the chemoprotective effects of this phytochemical. Full article

The objective of this study was to explore the mechanism of Hedyotis diffusa (HD) in mediating the detoxification of aflatoxin B₁ (AFB₁)-induced hepatic injury in chicks. A total of 144 one-day-old male broilers (Cobb 500) were randomly assigned to four treatment groups (n = 6 cages/diet, 6 chicks/cage). After three days of acclimation, the broilers were fed either a control diet (Control), Control plus 0.5 mg/kg of AFB₁, or Control plus 0.5 mg/kg AFB₁ with 500 or 1000 mg/kg HD for two weeks. Both serum and liver were collected at the end of the feeding trial for biochemistry, histology, and NF-E2-related nuclear factor 2 (NRF2)/antioxidant response element (ARE) signaling analysis. Compared with Control, the AFB₁ treatment caused liver injury and decreased (p < 0.05) body weight gain, feed intake, feed conversion ratio, and serum albumin and total protein by 6.2–20.7%. AFB₁ also induced swelling, necrosis, and severe vacuolar degeneration in chicks’ livers. Notably, HD supplementation at 500 and 1000 mg/kg mitigated (p < 0.05) the alterations induced by AFB₁. HD supplementation alleviated (p < 0.05) AFB₁-induced impairment in hepatic glutathione peroxidase activity, protein carbonyl, and exo-AFB₁-8,9-epoxide (AFBO)–DNA concentrations by 57.7–100% and increased (p < 0.05) the activities of superoxide dismutase and catalase by 23.1–40.9% more than those of AFB₁ treatment alone. Furthermore, HD supplementation at the two doses upregulated (p < 0.05) NRF2, NAD(P)H: quinone oxidoreductase-1, heme oxygenase-1, glutathione cysteine ligase catalytic subunit, and glutathione-S transferase A2 and A3 in livers relative to the AFB₁ group by 0.99–3.4-fold. Overall, dietary supplementation of HD at a high dose displayed better protection effects against aflatoxicosis. In conclusion, a dietary HD supplementation at 500 and 1000 mg/kg protected broilers from AFB₁-induced hepatotoxicity, potentially due to the activation of NRF2/ARE signaling in the chicks. Full article

This study was designed to establish if Curcumin (CM) alleviates Aflatoxin B₁ (AFB₁)-induced hepatotoxic effects and to determine whether alteration of the expression of cytochrome P450 (CYP450) isozymes is involved in the regulation of these effects in chick liver. One-day-old male broilers (n = 120) were divided into four groups and used in a two by two factorial trial in which the main factors included supplementing AFB₁ (< 5 vs. 100 μg/kg) and CM (0 vs. 150 mg/kg) in a corn/soybean-based diet. Administration of AFB₁ induced liver injury, significantly decreasing albumin and total protein concentrations and increasing alanine aminotransferase and aspartate aminotransferase activities in serum, and induced hepatic histological lesions at week 2. AFB₁ also significantly decreased hepatic glutathione peroxidase, catalase, and glutathione levels, while increasing malondialdehyde, 8-hydroxydeoxyguanosine, and exo-AFB₁-8,9-epoxide (AFBO)-DNA concentrations. In addition, the mRNA and/or activity of enzymes responsible for the bioactivation of AFB₁ into AFBO—including CYP1A1, CYP1A2, CYP2A6, and CYP3A4—were significantly induced in liver microsomes after 2-week exposure to AFB₁. These alterations induced by AFB₁ were prevented by CM supplementation. Conclusively, dietary CM protected chicks from AFB₁-induced liver injury, potentially through the synergistic actions of increased antioxidant capacities and inhibition of the pivotal CYP450 isozyme-mediated activation of AFB₁ to toxic AFBO. Full article