RESUMO
(1) Background: Regular exercise induces physiological and morphological changes in the organisms, but excessive training loads may induce damage and impair recovery or muscle growth. The purpose of the study was to evaluate the impact of Silymarin (SM) consumption on endurance capacity, muscle/cardiac histological changes, bodyweight, and food intake in rats subjected to 60 min of regular exercise training (RET) five days per week. (2) Methods: Male Wistar rats were subjected to an eight-week RET treadmill program and were previously administered SM and vitamin C. Bodyweight and food consumption were measured and registered. The maximal endurance capacity (MEC) test was performed at weeks one and eight. After the last training session, the animals were sacrificed, and samples of quadriceps/gastrocnemius and cardiac tissue were obtained and process for histological analyzes. (3) Results: SM consumption improved muscle recovery, inflammation, and damaged tissue, and promoted hypertrophy, vascularization, and muscle fiber shape/appearance. MEC increased after eight weeks of RET in all trained groups; moreover, the SM-treated group was enhanced more than the group with vitamin C. There were no significant changes in bodyweight and in food and nutrient consumption along the study. (5) Conclusion: SM supplementation may enhance physical performance, recovery, and muscle hypertrophy during the eight-week RET program.
Assuntos
Peso Corporal , Suplementos Nutricionais , Comportamento Alimentar , Músculo Esquelético/patologia , Miocárdio/patologia , Condicionamento Físico Animal , Desempenho Físico Funcional , Silimarina/farmacologia , Animais , Ácido Ascórbico/farmacologia , Peso Corporal/efeitos dos fármacos , Masculino , Músculo Esquelético/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Ratos Wistar , Silimarina/químicaRESUMO
Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300â¯mg/kg), N-acetylcysteine (200â¯mg/kg) or vehicle for 5â¯days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN.
Assuntos
Meios de Contraste/efeitos adversos , Rim/efeitos dos fármacos , Nefrite/induzido quimicamente , Nefrite/prevenção & controle , Substâncias Protetoras/uso terapêutico , Silimarina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Silybum marianum/química , Nefrite/metabolismo , Nefrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Silimarina/químicaRESUMO
PEGylated PAMAM-G4 dendrimers with substitution percentages of 50% and intermediate size PEG chains (0.55 and 2.0 kDa) were synthesized and evaluated as solubility enhancers and potential supramolecular carriers for the poorly soluble drug Silybin (SIL). Aqueous solubility profiles revealed that the PEGylated system with 2.0 kDa chains induced a five-fold solubility increase for SIL and the largest drug-loading capacity within the systems under study with an average complex stoichiometry of 71:1 according to the Higuchi-Connors formulation for multiple binding sites. The supramolecular interaction between SIL and PEGylated PAMAM-G4 dendrimers was confirmed by 2D-NOESY experiments, which evidenced the simultaneous complexation of the drug in both PAMAM-G4 branches and outermost PEG chains. In vitro release studies showed that 2.0 kDa PEG chains induced a more extended release time compared with 0.5 kDa PEG chains. This result was attributed to the enhancement of PEG assistance to SIL complexation in systems with longer PEG chains, which are able to self-penetrate into dendrimer cavities and cooperate in the stabilization of SIL complexes, thus delaying the release of SIL from the supramolecular host. These results are valuable for the future design and development of novel PAMAM-based systems for SIL complexation and delivery.
Assuntos
Antioxidantes/administração & dosagem , Dendrímeros/química , Portadores de Fármacos/química , Nylons/química , Polietilenoglicóis/química , Silimarina/administração & dosagem , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/toxicidade , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Células HEK293 , Humanos , Nylons/toxicidade , Polietilenoglicóis/toxicidade , Silibina , Silimarina/química , SolubilidadeRESUMO
Silibinin (SB) and pomegranate oil (PO) present therapeutic potential due to antioxidant activity, but the biological performance of both bioactives is limited by their low aqueous solubility. To overcome this issue, the aim of the present investigation was to develop nanocapsule suspensions with PO as oil core for SB encapsulation, as well as assess their toxicity in vitro and radical scavenging activity. The nanocapsule suspensions were prepared by interfacial deposition of preformed polymer method. SB-loaded PO-based nanocapsules (SBNC) showed an average diameter of 157 ± 3 nm, homogenous size distribution, zeta potential of -14.1 ± 1.7 mV, pH of 5.6 ± 0.4 and SB content close to 100%. Similar results were obtained for the unloaded formulation (PONC). The nanocapsules controlled SB release at least 10 times as compared with free SB in methanolic solution. The SBNC scavenging capacity in vitro was statistically higher than free SB (p < 0.05). Cell viability in monocytes and lymphocytes was kept around 100% in the treatments with SBNC and PONC, while the SB and the PO caused a decrease around 30% at 50 µM (SB) and 724 µg/mL (PO). Protein carbonyls and DNA damage were minimized by SB and PO nanoencapsulation. Lipid peroxidation occurred in nanocapsule treatments regardless of the SB presence, which may be attributed to PO acting as substrate in reaction. The free compounds also caused lipid peroxidation. The results show that SBNC and PONC presented adequate physicochemical characteristics and low toxicity against human blood cells. Thereby, this novel nanocarrier may be a promising formulation for therapeutic applications.
Assuntos
Citotoxinas/química , Sequestradores de Radicais Livres/química , Lythraceae , Nanocápsulas/química , Silimarina/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Citotoxinas/toxicidade , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/toxicidade , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Nanocápsulas/toxicidade , Óleos de Plantas/química , Óleos de Plantas/toxicidade , Silibina , Silimarina/toxicidade , SolubilidadeRESUMO
The present study shows the development of a topical formulation (hydrogel) containing silibinin-loaded pomegranate oil based nanocapsules suspension and its evaluation as an alternative for the treatment of cutaneous UVB radiation-induced damages. For this, an animal model of skin injury induced by UVB radiation was employed. Gellan gum was used as gel forming agent by its direct addition to nanocapsules suspension. The hydrogels showed adequate pH values (5.6-5.9) and a silibinin content close to the theoretical value (1mg/g). Through vertical Franz diffusion cells it was demonstrated that nanocapsules decreased the silibinin retention in the semisolid formulation. All formulations were effective in reducing mice ear edema and leukocyte infiltration induced by UVB radiation 24h after the treatments. After 48h, only the hydrogels containing nanocapsules or silibinin associated with pomegranate oil demonstrated anti-edematogenic effect, as well as the positive control (hydrogel containing silver sulfadiazine 1%). After 72h, the hydrogel containing unloaded pomegranate oil based nanocapsules still presented a small activity. In conclusion, the results of this investigation demonstrated the feasibility to prepare a semisolid formulation presenting performance comparable to the traditional therapeutic option for skin burns (silver sulfadiazine) and with prolonged in vivo anti-inflammatory activity compared to the non-nanoencapsulated compounds.
Assuntos
Anti-Inflamatórios/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanocápsulas/química , Óleos de Plantas/química , Silimarina/química , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Concentração de Íons de Hidrogênio , Lythraceae/química , Lythraceae/metabolismo , Masculino , Camundongos , Peroxidase/metabolismo , Sulfadiazina de Prata/uso terapêutico , Silibina , Silimarina/uso terapêutico , Pele/metabolismo , Pele/patologiaRESUMO
PAMAM-grafted TiO2 nanotubes (PAMAM-TiO2NT) have been synthesized and evaluated as new drug nanocarriers, using curcumin (CUR), methotrexate (MTX), and silibinin (SIL) as model therapeutic compounds. TiO2NT were surface-modified using a silane coupling agent and subsequently conjugated with PAMAM dendrimer of the third generation. The characterization of PAMAM-TiO2NT nanomaterials was performed by FTIR, TEM, N2 adsorption-desorption isotherms, XRD, and TGA techniques, which accounted for a 2.6wt.% of PAMAM grafting in the prepared materials. The drug loading capacity, drug release properties, and cytotoxicity of PAMAM-TiO2NT showed a significant improvement compared to pristine TiO2NT, thus revealing the promising properties of these new materials for drug delivery purposes.
Assuntos
Dendrímeros/química , Portadores de Fármacos/química , Nanotubos/química , Preparações Farmacêuticas/química , Titânio/química , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/metabolismo , Curcumina/toxicidade , Liberação Controlada de Fármacos , Células HeLa , Humanos , Metotrexato/química , Metotrexato/metabolismo , Metotrexato/toxicidade , Microscopia Eletrônica de Transmissão , Preparações Farmacêuticas/metabolismo , Silibina , Silimarina/química , Silimarina/metabolismo , Silimarina/toxicidade , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na2[VO(silibinin)22]·6H2O (VOsil) and chrysin [VO(chrysin)2EtOH]2(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Complexos de Coordenação/química , Flavonoides , Silimarina , Vanádio , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Complexos de Coordenação/farmacologia , Flavonoides/química , Humanos , Estrutura Molecular , Silibina , Silimarina/química , Vanádio/químicaRESUMO
Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line.
Assuntos
Anti-Infecciosos , Bactérias/crescimento & desenvolvimento , Candida/crescimento & desenvolvimento , Silimarina , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Relação Dose-Resposta a Droga , Silibina , Silimarina/química , Silimarina/farmacologiaRESUMO
Photodynamic Therapy (PDT) is an anticancer treatment based on photosensitisation of malignant cells. The precursor of the photosensitiser Protoporphyrin IX, 5-aminolevulinic acid (ALA), has been used for PDT of bladder cancer. Silybin is a flavonoid extracted from Silybum marianum, and it has been reported to increase the efficacy of several anticancer treatments. In the present work, we evaluated the cytotoxicity of the combination of ALA-PDT and silybin in the T24 and MB49 bladder cancer cell lines. MB49 cells were more sensitive to PDT damage, which was correlated with a higher Protoporphyrin IX production from ALA. Employing lethal light doses 50% (LD50) and 75% (LD75) and additional silybin treatment, there was a further increase of toxicity driven by PDT in both cell lines. Using the Chou-Talalay model for drug combination derived from the mass-action law principle, it was possible to identify the effect of the combination as synergic when using LD75, whilst the use of LD50 led to an additive effect on MB49 cells. On the other hand, the drug combination turned out to be nearly additive on T24 cells. Apoptotic cell death is involved both in silybin and PDT cytotoxicity in the MB49 line but there is no apparent correlation with the additive or synergic effect observed on cell viability. On the other hand, we found an enhancement of the PDT-driven impairment of cell migration on both cell lines as a consequence of silybin treatment. Overall, our results suggest that the combination of silybin and ALA-PDT would increase PDT outcome, leading to additive or synergistic effects and possibly impairing the occurrence of metastases.
Assuntos
Apoptose/efeitos dos fármacos , Fármacos Fotossensibilizantes/toxicidade , Silimarina/farmacologia , Ácido Aminolevulínico/química , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/toxicidade , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Luz , Silybum marianum/química , Silybum marianum/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Silibina , Silimarina/química , Silimarina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
A new complex of the oxovanadium(IV) cation with the flavolignan silibinin has been synthesized and characterized. Vanadium compounds show interesting biological and pharmacological properties and some of them display antitumoral actions. Flavonoids are part of a larger group of antioxidant compounds called polyphenols which may inhibit the proliferation and growth of cancer cells. The antioxidant and antitumoral effects of silibinin and its oxovanadium(IV) complex were investigated. Silibinin acted as a very strong antioxidant and its complexation with oxovanadium(IV) improved this behavior. Besides, the generation of reactive oxygen species (ROS) by this compound was favored in tumoral (UMR106) cells and correlated with the deleterious behavior in the proliferation of this cell line. Conversely, silibinin did not exert any effect on the proliferation of normal osteoblasts (MC3T3E1). The cytotoxic action and ROS generation of the oxovanadium(IV) complex was more effective in tumoral cells. This behavior was not consistent with cleaving DNA of plasmid DNA pA1 because no significant cleaving activity was observed in both cases. These results suggest that the main deleterious mechanisms may take place through cytotoxic effects more than genotoxic actions. A comparison with our own findings on the behavior of other flavonoids and their vanadyl(IV) complex has also been performed.