Properties of silibinin and of antioxidants against adriamycin cytotoxicity in a unicellular eukaryote, Tetrahymena thermophila

Soose, Mechthild

doi:10.1016/s0932-4739(11)80214-2

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…An interesting study of interaction of silybin and adriamycin in the unicellular eukaryote Tetrahymena thermophila demonstrated that silybin (1 mg/ml) completely prevents effects of adriamycin on the cell and biomass production 44 . Adriamycin transport to the cells was not inhibited by silybin.…”

Section: Silybin/silymarin In Adjuvant Therapy Of Cancermentioning

confidence: 99%

Silybin and silymarin - new effects and applications

Křen¹,

Walterová²

2005

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

371

233

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This article aims to review critically literature published mainly within this millennium on the new and emerging applications of silymarin, the polyphenolic fraction from the seeds of Silybum marianum and its main component silybin. Silymarin and silybin used so far mostly as hepatoprotectants were shown to have other interesting activities as e.g., anticancer and canceroprotective. These activities were demonstrated in a large variety of illnesses of different organs as e.g., prostate, lungs, CNS, kidneys, pancreas and others. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new activities based on the specific receptor interaction were discovered-e.g., inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors and some others. New derivatives of silybin open new ways to its therapeutic applications. Pharmacology dealing with optically pure silybin diastereomers may suggest new mechanisms of its action.

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Section: Silybin/silymarin In Adjuvant Therapy Of Cancermentioning

confidence: 99%

Silybin and silymarin - new effects and applications

Křen¹,

Walterová²

2005

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

371

233

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“…This increase was significantly less pronounced in animals that had received silibinin before DDP (Figure 2). (Valenzuela and Guerra, 1985;Soose, 1994). Another mechanism of renal toxicity of DDP may be the depression of DNA, RNA and protein synthesis as demonstrated in studies, in vitro (Tay et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Silibinin protects against cisplatin-induced nephrotoxicity without compromising cisplatin or ifosfamide anti-tumour activity

Bokemeyer

Fels²,

Dunn³

et al. 1996

Br J Cancer

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Summary Cisplatin is one of the most active cytotoxic agents in the treatment of testicular cancer, but its clinical use is associated with side-effects such as ototoxicity, neurotoxicity and nephrotoxicity. Long-term kidney damage from cisplatin particularly affects the proximal tubular apparatus and can be detected by increased urinary excretion of brush-border enzymes, such as L-alanine-aminopeptidase (AAP), and magnesium. In the current study, the flavonoid silibinin was used as a nephroprotectant for cisplatin-induced nephropathy in a rat animal model. Infusion of silibinin before cisplatin results in a significant decrease in glomerular (indicated by creatinine clearance and serum urea level) and tubular kidney toxicity (excretion of brush-border enzymes and magnesium). Silibinin given alone had no effect on renal function. In order to exclude an inhibition of the anti-tumour activity of cisplatin and 4-hydroperoxy-ifosfamide by coadministration of silibinin, in vitro studies were performed in three established human testicular cancer cell lines. Dose-response curves for cisplatin (3-30 000 nmol) combined with non-toxic silibinin doses (7.25 x 10-6 or 7.25 x 10-5 mol 1-1) did not deviate significantly from those of cisplatin alone as measured by relative cell survival during a 5 day assay using the sulphorhodamine-B staining technique. Also silibinin did not influence the cytotoxic activity of 4-hydroperoxy-ifosfamide (30-10 000 nmol) in vitro. In summary, these in vitro data rule out a significant inhibition of the anti-tumour activity of the major nephrotoxic components, cisplatin and 4-hydroperoxy-ifosfamide, by co-administration of silibinin in a human germ cell tumour cell line model. Together with these demonstrated cytoprotection effects in the rat animal model, these data form the basis for a randomised clinical trial of silibinin for the protection of cisplatin-associated nephrotoxicity in patients with testicular cancer.

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“…This cellular membrane could response more rapidly to the change of the outside environment than higher animals [4]. Because its growth curve corresponds with the representative growth curve of microbes, the reaction of T.t.BF 5 to the surrounding toxicant could be studied by analyzing the dynamic thermal growth curves.T.t.BF 5 has been applied in the fields of biology, pharmacy, toxicology, environment and polluted water evaluation as a perfect model [5][6][7][8][9]. However, few reports showed that it was applied to evaluate the toxicity of the solubilizing excipients of injection.…”

mentioning

confidence: 99%

“…T.t.BF 5 has been applied in the fields of biology, pharmacy, toxicology, environment and polluted water evaluation as a perfect model [5][6][7][8][9]. However, few reports showed that it was applied to evaluate the toxicity of the solubilizing excipients of injection.…”

mentioning

confidence: 99%

The toxic effect of solubilizing excipients on Tetrahymena thermophila BF5 growth investigated by microcalorimetry

et al. 2010

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The toxic effect of different solubilizing excipients on the growth and metabolism of Tetrahymena thermophila BF 5 (T.t.BF 5 ) at various concentrations was investigated by microcalorimetry. The thermogenic curves of T.t.BF 5 growth were determined at 28°C, and were evaluated by dynamic parameters. The results indicated that the values of growth rate constant (k), maximum power (P 1 , P 2 ), peak time (T 1 , T 2 ) and total quantity of heat (Q) varied for different excipients. There was a good linear relationship between k and concentrations (r>0.95, P<0.01). 5% inhibition concentration (IC 5 ) of poloxamer 188, Tween 80, PEG 600, PEG 400 and Tween 20 was 2.18, 1.07, 1.35, 0.58, and 0.045 mg/mL, respectively. After the principal component analysis (PCA), Q, k and P 1 could characterize the effect of these excipients on T.t.BF 5 growth. Comprehensive evaluation indicated that compared with the control group, poloxamer 188 had the weakest toxicity and Tween 20 had the strongest toxicity. solubilizing excipients, Tetrahymena thermophila BF 5 , microcalorimetry, IC 5 , PCA Citation: Zhang S F, Yan D, Tang H Y, et al. The toxic effect of solubilizing excipients on Tetrahymena thermophila BF 5 growth investigated by microcalorimetry.As nonionics, the structure of solubilizing excipients includes not only hydrophilic groupings, but also lipophilic groupings to form micelles or reverse micelles in the solution. Therefore, the solubilizing excipients could be used in the indissolvable liquid preparation as solubilizers or emulsifiers [1]. However, different biologic toxicities are possibly produced due to the excipient itself or the byproduct such as the ekibon, ethylene alcohol, and diethylene glycol. The security problems of the excipients, especially applied to the injection, seem to be serious. The general evaluation methods supply direct and apparent results for security evaluation of the solubilizing excipients [2], but shortcomings such as strong subjectivity and less sensitivity make the evaluation hard to be objective and quantifiable. It is necessary to develop an objective and sensitive method to evaluate biological security of the solubilizing excipients.T.t.BF 5 is a type of eukaryotic protozoa living in the fresh water which solely contains one cell. It has a representative subcellular structure which is seen among most of the eucaryons. It has similarities with cells of higher animals [3]. It contacts the outside environment through cellular membranes without cell walls. This cellular membrane could response more rapidly to the change of the outside environment than higher animals [4]. Because its growth curve corresponds with the representative growth curve of microbes, the reaction of T.t.BF 5 to the surrounding toxicant could be studied by analyzing the dynamic thermal growth curves.T.t.BF 5 has been applied in the fields of biology, pharmacy, toxicology, environment and polluted water evaluation as a perfect model [5][6][7][8][9]. However, few reports showed that it was applied to evaluate the toxicity ...

show abstract

Properties of silibinin and of antioxidants against adriamycin cytotoxicity in a unicellular eukaryote, Tetrahymena thermophila

Cited by 8 publications

References 40 publications

Silybin and silymarin - new effects and applications

Silybin and silymarin - new effects and applications

Silibinin protects against cisplatin-induced nephrotoxicity without compromising cisplatin or ifosfamide anti-tumour activity

The toxic effect of solubilizing excipients on Tetrahymena thermophila BF5 growth investigated by microcalorimetry

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