Javad Behravan

Curcumin potentiates doxorubicin-induced apoptosis in H9c2 cardiac muscle cells through generation of reactive oxygen species

Doxorubicin (DOX) is a widely used chemotherapy agent. The major adverse effect of DOX treatment in cancer patients is the onset of cardiomyopathy and heart failure. Reactive oxygen species (ROS) are proposed to be responsible for DOX cardiotoxicity. Curcumin, a natural compound extracted from Curcuma Longa L., is known for its anti-oxidant properties. It has been identified as increased apoptosis in several cancer cell lines in combination with doxorubicin, but there are few studies about the effect of curcumin and doxorubicin on normal cardiac cells. Therefore, we evaluated the effects of curcumin on apoptosis induced by DOX in cardiac muscle cells. Pretreatment with curcumin significantly increased DOX-induced apoptosis of cardiac muscle cells through down regulation of Bcl-2, up-regulation of caspase-8 and caspase-9. The Bax/Bcl-2 ratio increased significantly after 1h pretreatment with curcumin. As well, curcumin increases ROS generation by DOX. In response to DOX, NF-κB was activated. However, curcumin was able to inhibit NF-κB activation. In conclusion, our results indicated that pretreatment with nontoxic concentrations of curcumin sensitized H9c2 cells to DOX-mediated apoptosis by generation of ROS.

Drug transport across the placenta, role of the ABC drug efflux transporters

The placenta serves an important role both as a protective barrier as well as in normal fetal development. The ATP-binding cassette (ABC) proteins perform crucial functions in the distribution of nutrients and exchange of waste metabolites across the placenta. They also protect the developing fetus from xenobiotics to which the pregnant mother is exposed. Recent studies in P-glycoprotein (P-gp) deficient mdr1a and mdr1b (-/-) CF-1 mice have shown pronounced increases in fetal exposure to P-gp substrates due to increased transplacental penetration demonstrating the important protective role of P-gp to the developing fetus. The role of placental ABC transporter proteins in protecting the fetus against maternal exposure to drugs, toxins and other xenobiotics is discussed. Overall, the paucity of information available on the transplacental transfer of drugs emphasizes the need to further employ preclinical in vivo models for drug development in order to best predict fetal outcomes of drug administration to pregnant mothers.

Targeted delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer

Application of daunorubicin in treatment of leukemia has been limited for its side effects like cardiotoxicity. Specific delivery of chemotherapy drugs is an important factor in decreasing their side effects. In this study, sgc8, an aptamer for protein tyrosine kinase-7 (PTK7), was used for specific delivery of daunorubicin to Molt-4 cells (PTK7+). Flow cytometric experiments showed that aptamer–daunorubicin complex was internalized effectively to Molt-4 cells (PTK7+), but not to U266 cells (PTK7−). This fact was confirmed by less cytotoxicity of aptamer–drug complex in U266 cells in compare to daunorubicin alone. No significant change in viability between daunorubicin and aptamer–daunorubicin complex treated Molt4 cells was observed. In conclusion, sgc8-daunorubicin complex is introduced as a simple and efficient system for targeted delivery of drug to acute lymphoblastic leukemia T cells.

Composition, Antimycotic and Antibacterial Activity of Ziziphora clinopodioides Lam. Essential Oil from Iran

Abstract The essential oil components of Ziziphora clinopodioides Lam. from Iran were isolated via hydrodistillation and analyzed by GC-MS. Twenty seven components were identified in the essential oil of the plant. The main compounds consisted of pulegone (44.5 %), terpineol (14.5%) methyl acetate (10.9%), iso-neomenthol (7.1%) and 1, 8-cineole (4.1%). Antifungal and antimicrobial acitivities of different concentrations of the essential oil of Ziziphora clinopodioides Lam. was also evaluated. The antifungal tests were conducted by a poisoned food technique against the filamentous fungi (Aspergillus niger, Trichophyton rubrum, Trichoderma reesei and Microsporum gypseum). antimicrobial tests were carried out against four Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumonia) and one Gram positive pathogen (Staphyloccocus aureus) using a microdilution assay. The essential oil was found to be fungicidal at >1 μl/ml against T. rubrum and M. gypseum. The minimum inhibitory concentration of the oil against Escherichia coli, Staphyloccocus aureus, Pseudomonas aeruginosa, Salmonella typhi and Kleb-siella pneumonia were found to be 0.003, 0.033, 0.033, 0.067 and 0.067 % (v/v) respectively.

Interleukin-1 beta and tumor necrosis factor-alpha increase ABCG2 expression in MCF-7 breast carcinoma cell line and its mitoxantrone-resistant derivative, MCF-7/MX.

ObjectiveIn this study, we aimed to evaluate the influence of proinflammatory cytokines on ABCG2 expression and function in human MCF-7 breast cancer cell line and its mitoxantrone-resistant derivative MCF-7/MX.MethodsThe effects of proinflammatory cytokines on ABCG2 mRNA expression were studied using real-time PCR method. Cytokine-mediated modification of ABCG2 protein expression and function was investigated by means of flow cytometry.ResultsSignificant inductions in the ABCG2 mRNA levels, protein expression, and activity were observed in IL-1β and TNF-α-treated MCF-7 cells. IL-6 increased ABCG2 protein, but had no effects on ABCG2 mRNA and function in MCF-7 cells. Although IL-1β did not alter mRNA and protein levels of the transporter in MCF-7/MX cells, ABCG2-mediated efflux was significantly increased in IL-1β-treated MCF-7/MX cells. TNF-α-treated MCF-7/MX cells also demonstrated greater ABCG2 protein expression and function without any changes in mRNA levels of the transporter. Neither ABCG2 mRNA nor its protein expression and function were affected by IL-6 in MCF-7/MX cells.ConclusionIL-1β and TNF-α induce ABCG2 mRNA and protein expression and increase its activity in breast cancer cell line MCF-7. In MCF-7/MX cells these cytokines modulate ABCG2 protein expression and/or function, but they have no influence on the transporter mRNA levels.

Survey of bacteriological contamination of cosmetic creams in Iran (2000).

The bacteriological quality of a variety of unused and used cosmetic creams was investigated. A 1‐g sample from each product was aseptically placed in 9 ml of sterile Tween‐peptone diluent, and 10‐fold serial dilutions were prepared. The pour plate technique was used for aerobic bacterial colony counts, and microorganisms that grew in the culture were identified. The incidence of contamination by Gram‐positive Bacilli, Staphylococcus aureus and non Escherichia coli Gram‐negative organisms was found to be higher for used cosmetic creams (54%, 38% and 8%, respectively) than for unused creams (38%, 25% and 0%, respectively). Viable microorganisms were not recovered from 17% of the unused items whilst only 10% of the used creams did not contain viable microorganisms. The significance of the results is discussed and the importance of adopting suitable quality control guidelines is highlighted.

Protective effects of aqueous and ethanolic extracts of Portulaca oleracea L. aerial parts on H2O2-induced DNA damage in lymphocytes by comet assay.

The comet assay is a standard method for measuring DNA damage. In this study, the protective effects of ethanolic and aqueous extracts of Portulaca oleracea L. (P. oleracea) on human lymphocyte DNA lesions were evaluated with the comet assay. Lymphocytes were isolated from blood samples taken from healthy volunteers. Human lymphocytes were incubated in H(2)O(2) (50,100, and 200 μM), aqueous extract (0.05, 0.1, 0.5, 1, and 2.5mg/ml), and ethanolic extracts (0.05, 0.1, 0.5, 1, and 2.5mg/ml) of P. oleraceae aerial parts alone with a combination of H(2)O(2) (100 μM) with either 1 or 2.5mg/ml of both extracts at 4°C for 30 minutes. The extent of DNA migration was measured using the alkaline single cell gel electrophoresis approach assay, and DNA damage was expressed as percentage tail DNA. We found that the aqueous extract of P. oleracea significantly inhibited DNA damage, while there was no effect of the ethanolic extract. These data suggest that the aqueous extract of P. oleracea can prevent oxidative DNA damage to human lymphocytes, which is likely due to antioxidant constituents in the extract.

Optimization of dextran production by Leuconostoc mesenteroides NRRL B‐512 using cheap and local sources of carbohydrate and nitrogen

Using pure components for the fermentation medium in dextran production imposes high costs on the industry. In the present study, the economic production of dextran using local and cheap sources of carbohydrate and nitrogen was investigated. Different concentrations of molasses and wheat‐bran extract, after filtration, steam sterilization and pH adjustment, were inoculated with a fresh suspension of Leuconostoc mesenteroides. Cultures were incubated, and then diluted with an equal volume of ethanol. The bacteria were pelleted, and an aliquot of the supernatant was diluted with ethanol and dextran was precipitated. The supernatant was removed and the precipitate was dissolved in a minimal volume of water. Activated charcoal was added and the solution was boiled. The solution was filtered and protein impurities removed by 2‐methylbutan‐2‐ol/chloroform extraction. Dextran was again precipitated with cold ethanol as described above, and the precipitate was dried in a desiccator. Optimum conditions and composition of culture media for dextran production using sugar‐beet molasses and wheat bran were determined. The best results were obtained when 20% (w/v) molasses and 15% (w/v) wheat bran were used. The optimal initial pH for dextran production was 7.5.

CHEMICAL COMPOSITION AND ANTIMICROBIAL ACTIVITY OF THE VOLATILE OIL OF ARTEMISIA KHORASSANICA FROM IRAN

Abstract Artemisia khorassanica. Podl. (Asteraceae) is a common perennial herb growing wild in northeastern parts of Iran. The essential oil of A. khorasanica. was isolated by hydrodistillation in 1.25 (v/w) yield. The chemical composition of the essential oil was examined by gas chromatography and gas chromatography-mass spectrometry. Thirty-one compounds were identified, representing 79.6% of the total oil. The major constituents were 1,8-cineol (17.7%), camphor (13.9%), davanone (12.2%), and isogeraniol (5.7%). Minimum inhibitory concentration was determined using agar dilution method against eight bacteria and two fungal strains. The essential oil indicated a moderate antimicrobial activity.

Auraptene from Ferula szowitsiana protects human peripheral lymphocytes against oxidative stress.

The antigenotoxicity effects of auraptene on DNA damage in human peripheral lymphocytes were studied using alkaline single cell gel electrophoresis. Auraptene at concentrations of 5, 10, 25, 50, 100, 200 and 400 µM was tested under simultaneous treatment with 25 µM H2O2. The data are expressed as % tail DNA and compared with ascorbic acid at concentrations of 25, 50, 100, 200 and 400 µM. Auraptene significantly reduced the genotoxicity of H2O2 at concentrations higher than 25 µM (p < 0.001). Interestingly, the antigenotoxicity activity of auraptene was higher than ascorbic acid (p < 0.01), however, at some concentrations (25, 50 and 200 µM) there was no significant difference between auraptene and ascorbic acid (p > 0.05). It seems that the significant antigenotoxicity effects of auraptene may be due to the prenyl moiety and also the suppression of superoxide anion (O2−) generation. This study suggests that the antigenotoxic property of auraptene is of great pharmacological importance and might be beneficial for cancer prevention. Copyright