Crosstalk between E2F1 and P53 transcription factors in doxorubicin-induced DNA damage: evidence for preventive/protective effects of silymarin

Abstract

DOX-induced testicular toxicity was characterized by lowering sperm quality values, induction of oxidative and nitrosative stress and DNA fragmentation. Preventive and protective effects of SMN on DOX-induced testicular toxicity may attribute to its antioxidant property. DOX-induced testicular damages and SMN preventive/protective effects might be mediated via up- and down-regulation of p53 and E2F1 transcription factors.

Effect of Cucumis sativus on Dysfunctional 3T3-L1 Adipocytes

“…These combinations were evaluated in their anti-oxidant and anti-inflammatory capacity; according to our results, two combinations (M4 and M5) exhibited anti-inflammatory effects (decreased IL-6 levels, Fig. 7A) and anti-oxidant effects (decreased O 2 • − levels) similar to those of silymarin, a flavonoid with well-documented anti-oxidant and anti-inflammatory activity 44–46 .…”

“…Once adipocyte dysfunction was established as described below, five concentrations (5, 10, 20, 40, or 80 μg/mL) of the three Aq-Cs SFs (SF1, SF2, and SF3) were added to the culture and allowed to stand for 24 h. Either silymarin (50 μg/mL) 50,51 or metformin (1 mM) 52,53 were used as positive controls; previous reports have employed these molecules as standard drug: for silymarin as control of oxidative stress and the inflammatory condition induced by the presence of IL-1β 45,46 . For Metformin it was used as control of glucose consumption and the accumulation of lipids in adipocytes, functions that were affected by the presence of dexamethasone 27–30 .…”

Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer

“…It has been also shown that silymarin coadministration with chemotherapeutic agents has, often, a protective effect in reducing chemotherapeutic toxicities in normal organs (Fanoudi, Alavi, Karimi, & Hosseinzadeh, ). For example, animals receiving DOX were shown to have p53 expression up‐regulated and E2F1 down‐regulated at mRNA level, which could be reserved following silymarin administration (Shafiei‐Roudbari, Malekinejad, Janbaz‐Aciabar, & Razi, ). Furthermore, silymarin significantly reduced DOX‐induced sperm abnormalities, as well as DNA fragmentation and NO concentration (Shafiei‐Roudbari et al, ).…”

“…For example, animals receiving DOX were shown to have p53 expression up‐regulated and E2F1 down‐regulated at mRNA level, which could be reserved following silymarin administration (Shafiei‐Roudbari, Malekinejad, Janbaz‐Aciabar, & Razi, ). Furthermore, silymarin significantly reduced DOX‐induced sperm abnormalities, as well as DNA fragmentation and NO concentration (Shafiei‐Roudbari et al, ). Also, it increased total antioxidant power, rate of sperm motility, and viability in animal models.…”

“…Also, it increased total antioxidant power, rate of sperm motility, and viability in animal models. Thus, it is feasible to state that silymarin can exert preventive and protective effects on DOX‐induced testicular toxicity through its antioxidant activity (Shafiei‐Roudbari et al, ).…”