Protective Effects of Silymarin and Silibinin against DNA Damage in Human Blood Cells

Borges, Flávio Fernandes Veloso; Silva, Carolina Ribeiro e; Goes, Wanessa Moreira; Godoy, Fernanda Ribeiro; Franco, Fernanda Craveiro; Véras, Jefferson Hollanda; Bailão, Elisa Flávia Luiz Cardoso; Silva, Daniela de Melo e; Cardoso, Cléver Gomes; Cruz, Aparecido Divino da; Chen-Chen, Lee

doi:10.1155/2018/6056948

Cited by 13 publications

(7 citation statements)

References 35 publications

(38 reference statements)

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“…In the study of Togay et al [100], DNA damage in rats with streptozotocin-induced diabetes symptoms were decreased after silibinin treatment. Similarly, Fernandes Veloso Borges et al [101] showed that silibinin (5.2-15.5 mM) reduced the amount of DNA in the comet tail compared to positive control. Silibinin is known to exhibit strong antioxidant activities and its protective effects against ROS have been demonstrated in different cell lines [41,42].…”

Section: Protective Effects Of Silibinin Against Mycotoxin Genotoxicitymentioning

confidence: 85%

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Tran

Viktorová

Augustynkova

et al. 2020

Toxins

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Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.

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Section: Protective Effects Of Silibinin Against Mycotoxin Genotoxicitymentioning

confidence: 85%

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Tran

Viktorová

Augustynkova

et al. 2020

Toxins

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“…Instead, at their physiological nontoxic concentrations, they maintain nucleophilic tonus by a mechanism called “para-hormesis” leading to the activation of the transcription of the antioxidant enzymes, which leads to protection and activation of repair mechanisms [33]. This type of silymarin action was reported; specifically the ability to prevent DNA damage in human blood cells [34] or to increase the antioxidant enzyme transcription in animals [35].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives

et al. 2019

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Silychristin A is the second most abundant compound of silymarin. Silymarin complex was previously described as an antioxidant with multidrug resistance modulation activity. Here, the results of a classical biochemical antioxidant assay (ORAC) were compared with a cellular assay evaluating the antioxidant capacity of pure silychristin A and its derivatives (anhydrosilychristin, isosilychristin and 2,3-dehydrosilychristin A). All the tested compounds acted as antioxidants within the cells, but 2,3-dehydro- and anhydro derivatives were almost twice as potent as the other tested compounds. Similar results were obtained in LPS-stimulated macrophages, where 2,3-dehydro- and anhydrosilychristin inhibited NO production nearly twice as efficiently as silychristin A. The inhibition of P-glycoprotein (P-gp) was determined in vitro, and the respective sensitization of doxorubicin-resistant ovarian carcinoma overproducing P-gp was detected. Despite the fact that the inhibition of P-gp was demonstrated in a concentration-dependent manner for each tested compound, the sensitization of the resistant cell line was observed predominantly for silychristin A and 2,3-dehydrosilychristin A. However, anhydrosilychristin and isosilychristin affected the expression of both the P-gp (ABCB1) and ABCG2 genes. This is the first report showing that silychristin A and its 2,3-dehydro-derivative modulate multidrug resistance by the direct inhibition of P-gp, in contrast to anhydrosilychristin and isosilychristin modulating multidrug resistance by downregulating the expression of the dominant transmembrane efflux pumps.

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“…In this study, CP administration caused a reduction in Bcl-2 level which is improved by SMN and MZN administration. As it upregulates the expression of Bcl-2, SMN has antigenotoxic properties and modulates the expression of genes involved in cell defense against DNA damage 29 .…”

Section: Discussionmentioning

confidence: 99%

Antioxidant, Anti-Inflammatory and Antiapoptotic Effect of Mirtazapine Mitigates Cyclophosphamide-Induced Testicular Toxicity in Rats

Mostafa-He¹,

Alanazi²,

Abdelmawll³

2023

International J. of Pharmacology

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Background and Objective: Cyclophosphamide (CP) is an anticancer drug that may result in organ toxicities, especially testicular toxicity.Mirtazapine (MTZ) is an antidepressant drug with antioxidant activities. Here in this study, the effect of the MTZ, silymarin or its combination against CP-induced testicular toxicity in rats was examined. Materials and Methods: Thirty male rats were classified into five groups: Group (1) represents the normal control group, group (2) represents the CP-treated group, group (3) represents the mirtazapine-treated group, group (4) represents the Silymarin-treated group and group (5) represent the combined mirtazapine and silymarin-treated group. Results: Compared to the normal control group, CP induced a significant decrease in testosterone, catalase, GSH, SOD, IL-10, eNOS, HO-1, Ki67 (IHC), Bcl-2 and a significant increase in MDA, ALK, IL-6, IL-1$ and TNF-" and iNOS. In addition, it altered the histological structure of the testis. Administration of MTZ, Silymarin, or its combinations significantly reverses CP-induced testicular toxicity and ameliorated histological changes of testis induced by CP administration. Conclusion: Results concluded that MTZ can protect against CP-induced testicular toxicity via its antiapoptotic, antioxidant and anti-inflammatory activities.

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Protective Effects of Silymarin and Silibinin against DNA Damage in Human Blood Cells

Cited by 13 publications

References 35 publications

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Antioxidant, Anti-Inflammatory, and Multidrug Resistance Modulation Activity of Silychristin Derivatives

Antioxidant, Anti-Inflammatory and Antiapoptotic Effect of Mirtazapine Mitigates Cyclophosphamide-Induced Testicular Toxicity in Rats

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