Search results for: drug induced premature chromosome condensation

Authors: Marwa T. Badawy, Alaa F. Bakr, Nesrine Hegazi, Mohamed A. Farag, Ahmed Abdellatif

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Diabetes Mellitus (DM) is a chronic disease affecting a large population worldwide. Africa is rich in native medicinal plants with myriad health benefits, though less explored towards the development of specific drug therapy as in diabetes. This study aims to determine the in vivo antidiabetic potential of the well-reported and traditionally used fruits of Baobab (Adansonia digitata L.) using STZ induced diabetic model. The in-vitro cytotoxic and antioxidant properties were examined using MTT assay on L-929 fibroblast cells and DPPH antioxidant assays, respectively. The extract showed minimal cytotoxicity with an IC50 value of 105.7 µg/mL. Histopathological and immunohistochemical investigations showed the hepatoprotective and the renoprotective effects of A. digitata fruits’ extract, implying its protective effects against diabetes complications. These findings were further supported by biochemical assays, which showed that i.p., injection of a low dose (150 mg/kg) of A. digitata twice a week lowered the fasting blood glucose levels, lipid profile, hepatic and renal markers. For a comprehensive overview of extract metabolites composition, ultrahigh performance (UHPLC) analysis coupled to high-resolution tandem mass spectrometry (HRMS/MS) in synchronization with molecular networks led to the annotation of 77 metabolites, among which 50% are reported for the first time in A. digitata fruits.

Keywords: adansonia digital, diabetes mellitus, metabolomics, streptozotocin, Sprague, dawley rats

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Authors: Manjusha Choudhary

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Objective: Cassia occidentalis Linn. belongs to Family Caesalpiniaceae is a common weed scattered from the foothills of Himalayas to West Bengal, South India, Burma, and Sri Lanka. It is used widely in folklore medicine in India as laxative, expectorant, analgesic, anti-malarial, hepatoprotective, relaxant, anti-inflammatory and antidiabetic. The present study was carried out to investigate the hypoglycaemic and hypolipidemic activities of ethanolic extract of Cassia occidentalis stem bark. Methods: Stem bark extract of Cassia occidentalis (SBCO) was administered orally at 250 and 500 mg/kg doses to normal and streptozotocin (STZ) induced type-2 diabetic mice. Various parameters like fasting blood glucose (FBG) level, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake were performed for the evaluation of antidiabetic effects. Results: Both the doses of extract caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. Administration of SBCO led to the decrease in the blood glucose, food intake, water intake, organ weight, SGOT, SGPT levels with significant value and increased the levels of TG, HDL cholesterol, creatinine, cholesterol, total protein with a significant value (p < 0.05-0.01). The decrease in body weight induced by STZ was restored to normal with a significant value (p < 0.01) at both doses. Conclusion: Present study reveals that SBCO possess potent hypoglycaemic and hypolipidemic activities and supports the folklore use of the stem bark of plant as antidiabetic agent.

Keywords: Cassia occidentalis, diabetes, folklore, herbs, hypoglycemia, streptozotocin

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Authors: Syed Asif Hassan, Syed Atif Hassan

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Multidrug-resistant Tuberculosis (MDR-TB) is an infection caused by the resistant strains of Mycobacterium tuberculosis that do not respond either to isoniazid or rifampicin, which are the most important anti-TB drugs. The increase in the occurrence of a drug-resistance strain of MTB calls for an intensive search of novel target-based therapeutics. In this context LprG (Rv1411c) a lipoprotein from MTB plays a pivotal role in the immune evasion of Mtb leading to survival and propagation of the bacterium within the host cell. Therefore, a machine learning method will be developed for generating a computational model that could predict for a potential anti LprG activity of the novel antituberculosis compound. The present study will utilize dataset from PubChem database maintained by National Center for Biotechnology Information (NCBI). The dataset involves compounds screened against MTB were categorized as active and inactive based upon PubChem activity score. PowerMV, a molecular descriptor generator, and visualization tool will be used to generate the 2D molecular descriptors for the actives and inactive compounds present in the dataset. The 2D molecular descriptors generated from PowerMV will be used as features. We feed these features into three different classifiers, namely, random forest, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model based on the accuracy of predicting novel antituberculosis compound with an anti LprG activity. Additionally, the efficacy of predicted active compounds will be screened using SMARTS filter to choose molecule with drug-like features.

Keywords: antituberculosis drug, classifier, machine learning, molecular descriptors, prediction

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Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer

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The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.

Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3

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Authors: Faisal Salah, Z. A. Aziz, K. K. Viswanathan

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In this article, the effects of g-jitter induced and combined with heat and mass transfer by mixed convection of MHD Maxwell fluid in microgravity situation is investigated for a simple system. This system consists of two heated vertical parallel infinite flat plates held at constant but different temperatures and concentrations. By using modified Darcy’s law, the equations governing the flow are modelled. These equations are solved analytically for the induced velocity, temperature and concentration distributions. Many interesting available results in the relevant literature (i.e. Newtonian fluid) is obtained as the special case of the present general analysis. Finally, the graphical results for the velocity profile of the oscillating flow in the channel are presented and discussed for different values of the material constants.

Keywords: g-jitter, heat and mass transfer, mixed convection, Maxwell fluid, porous medium

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Authors: Dhahri Maher, Aouinet Hana

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The presence of bubbles in the boundary layer introduces corrections into the log law, which must be taken into account. In this work, a logarithmic wall law was presented for bubbly two phase flows. The wall law presented in this work was based on the postulation of additional turbulent viscosity associated with bubble wakes in the boundary layer. The presented wall law contained empirical constant accounting both for shear induced turbulence interaction and for non-linearity of bubble. This constant was deduced from experimental data. The wall friction prediction achieved with the wall law was compared to the experimental data, in the case of a turbulent boundary layer developing on a vertical flat plate in the presence of millimetric bubbles. A very good agreement between experimental and numerical wall friction prediction was verified. The agreement was especially noticeable for the low void fraction when bubble induced turbulence plays a significant role.

Keywords: bubbly flows, log law, boundary layer, CFD

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Authors: Wassim Guermazi, Saoussan Boukhris, Neila Annabi Trabelsi, Tarek Rebai, Alya Sellami-Kamoun, Habib Ayadi

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This work investigates the protective effects of the microalga Halamphora sp. extract (H. Ext) as a natural product on lead-intoxicated liver and kidney human cells in vitro and in vivo on rats wistar. HepG2 cells line derived from human hepatocellular carcinoma and HEK293 cells line derived from human embryonic kidney were used for the in vitro study. The analysis of the fatty acids methyl esters of the extract was performed by a GC/MS. Four groups of rats, each of which was composed of six animals, were used for the in vivo experiment. The pretreatment of HepG2 and HEK293 cells line with the extract (100 µg mL-1) significantly (p < 0.05) protected against cytotoxicity induced by lead exposure. In vivo, the biochemical parameters in serum, namely malondialdehyde level (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, were measured in supernatants of organ homogenates. H. Ext was found to be rich in fatty acids, essentially palmitic and palmitoleic accounting respectively 29.46% and 42.07% of total fatty acids. Both in vitro and in vivo, the co-treatment with H. Ext allowed the protection of the liver and kidney cells structure, as well as the significant preservation of normal antioxidant and biochemical parameters in rats. Halamphora extract rich in fatty acids has been proven to be effective in protection against Pb-induced toxicity.

Keywords: microalga extract, human cells line, fatty acid, lead exposure, oxidative stress, rats

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Authors: Qing Cao, Fei Wang, Yu-Qiang Wang, Li-Ya Huang, Tian-Tian Sang, Shu-Yan Chen

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Aims: TNF Receptor-Associated Factor 6 (TRAF6) acts as a multifunctional regulator of the Transforming Growth Factor (TGF)-β signaling pathway, and mediates Smad-independent JNK and p38 activation via TGF-β. This study was performed to test the hypothesis that TGF-β/TRAF6 is essential for angiotensin-II (Ang II)-induced differentiation of rat c-kit+ Cardiac Stem Cells (CSCs). Methods and Results: c-kit+ CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-β type I receptor inhibitor (SB431542) or the small interfering RNA (siRNA)-mediated knockdown of TRAF6 were used to investigate the role of TRAF6 in TGF-β signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR deleted siRNA insensitive construct was conducted to rule out the off target effects of the siRNA. TRAF6 dominant negative (TRAF6DN) vector was constructed and used to infect c-kit+ CSCs, and western blotting was used to assess the expression of TRAF6, JNK, p38, cardiac-specific proteins, and Wnt signaling proteins. Physical interactions between TRAF6 and TGFβ receptors were studied by coimmunoprecipitation. Cardiac differentiation was suppressed in the absence of TRAF6. Forced expression of TRAF6 enhanced the expression of TGF-β-activated kinase1 (TAK1), and inhibited Wnt signaling. Furthermore, TRAF6 increased the expression of cardiac-specific proteins (cTnT and Cx-43) but inhibited the expression of Wnt3a. Conclusions: Our data suggest that TRAF6 plays an important role in Ang II induced differentiation of c-kit+ CSCs via the non-canonical signaling pathway.

Keywords: cardiac stem cells, differentiation, TGF-β, TRAF6, ubiquitination, Wnt

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Authors: Ahmed. Abdel Bary, Omneya. Khowessah, Mojahed. al-jamrah

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Introduction: The major challenge with the design of oral dosage forms lies with their poor bioavailability. The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability. The aim of this study was to develop solid nanodispersed tablet formulation of Glimepiride for the enhancement of the solubility and bioavailability. Methodology: Solid nanodispersions of Glimepiride (GMP) were prepared using two different ratios of 2 different carriers, namely; PEG6000, pluronic F127, and by adopting two different techniques, namely; solvent evaporation technique and fusion technique. A full factorial design of 2 3 was adopted to investigate the influence of formulation variables on the prepared nanodispersion properties. The best chosen formula of nanodispersed powder was formulated into tablets by direct compression. The Differential Scanning Calorimetry (DSC) analysis and Fourier Transform Infra-Red (FTIR) analysis were conducted for the thermal behavior and surface structure characterization, respectively. The zeta potential and particle size analysis of the prepared glimepiride nanodispersions was determined. The prepared solid nanodispersions and solid nanodispersed tablets of GMP were evaluated in terms of pre-compression and post-compression parameters, respectively. Results: The DSC and FTIR studies revealed that there was no interaction between GMP and all the excipients used. Based on the resulted values of different pre-compression parameters, the prepared solid nanodispersions powder blends showed poor to excellent flow properties. The resulted values of the other evaluated pre-compression parameters of the prepared solid nanodispersion were within the limits of pharmacopoeia. The drug content of the prepared nanodispersions ranged from 89.6 ± 0.3 % to 99.9± 0.5% with particle size ranged from 111.5 nm to 492.3 nm and the resulted zeta potential (ζ ) values of the prepared GMP-solid nanodispersion formulae (F1-F8) ranged from -8.28±3.62 mV to -78±11.4 mV. The in-vitro dissolution studies of the prepared solid nanodispersed tablets of GMP concluded that GMP- pluronic F127 combinations (F8), exhibited the best extent of drug release, compared to other formulations, and to the marketed product. One way ANOVA for the percent of drug released from the prepared GMP-nanodispersion formulae (F1- F8) after 20 and 60 minutes showed significant differences between the percent of drug released from different GMP-nanodispersed tablet formulae (F1- F8), (P<0.05). Conclusion: Preparation of glimepiride as nanodispersed particles proven to be a promising tool for enhancing the poor solubility of glimepiride.

Keywords: glimepiride, solid Nanodispersion, nanodispersed tablets, poorly water soluble drugs

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Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany

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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.

Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor

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Authors: Nilamadhab Mohanty

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It is essential to use message formats that make communication understandable and correct. It is because; the information format can influence consumer decision on the purchase of a product. This study combines information from qualitative inquiry, media trend analysis, eye tracking experiment, and questionnaire data to examine the impact of specific message format and consumer perceived risk on attention to the information and risk retention. We investigated the influence of message framing (goal framing, attribute framing, and mix framing) on consumer memory, study time, and decisional uncertainty while deciding on the purchase of drugs. Furthermore, we explored the impact of consumer perceived risk (associated with the use of the drug, i.e., RISK-AB and perceived risk associated with the non-use of the drug, i.e., RISK-EB) on message format preference. The study used eye-tracking methods to understand the differences in message processing. Findings of the study suggest that the message format influences information processing, and participants' risk perception impacts message format preference. Eye tracking can be used to understand the format differences and design effective advertisements.

Keywords: message framing, consumer perceived risk, advertising, eye tracking

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Authors: Jadranka Blazhevska Gilev

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IR laser-induced ablation of poly(butylacrylate-methylmethacrylate/hydroxyl ethyl methacrylate)/reduced graphene oxide (p(BA/MMA/HEMA)/rGO) was examined with 0.5, 0.75 and 1 wt% reduced graphene oxide content in relation to polymer. The irradiation was performed with TEA (transversely excited atmosphere) CO₂ laser using incident fluence of 15-20 J/cm², repetition frequency of 1 Hz, in an evacuated (10-3 Pa) Pyrex spherical vessel. Thin deposited nanocomposites films with large specific area were obtained using different substrates. The properties of the films deposited on these substrates were evaluated by TGA, FTIR, (Thermogravimetric analysis, Fourier Transformation Infrared) Raman spectroscopy and SEM microscopy. Homogeneous distribution of graphene sheets was observed from the SEM images, making polymer/rGO deposit an ideal candidate for SERS application. SERS measurements were performed using Rhodamine 6G as probe molecule on the substrate Ag/p(BA/MMA/HEMA)/rGO.

Keywords: laser ablation, reduced graphene oxide, polymer/rGO nanocomposites, thin deposited film

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Authors: Myung Kwon Cho, Seul Ki Min, Gwang Heum Yoon, Jung Hyun Joo, Sang Jun Sim, Hwa Sung Shin

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Mechanotransduction is a mechanism that external mechanical stimulation is converted to biochemical activity in the cell. When applying this mechanism to the unicellular green algae Chlamydomonas reinhardtii, the dramatic result that the accumulation of intracellular lipid was up to 60% of dry weight basis occurred. Furthermore, various variations in cellular physiology occurred, but there is a lack of the development of the system and related research for applying that technology to control the mechanical stress and facilitate molecular analyses. In this study, applying a mechanical stress to microalgae, the microfluidic device system that finely induced direct membrane distortion of microalgae. Cellular membrane distortion led to deflagellation, calcium influx and lipid accumulation in microalgae. In conclusion, cytological studies such as mechanotransduction can be actualized by using this system and membrane distortion is a promising inducer for biodiesel production.

Keywords: mechanotransduction, microalgae, membrane distortion, biodiesel

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Authors: Hua Li, Hongwu Deng

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The turbine blade's leading edge is usually cooled by jet impingement cooling technology due to the heaviest heat load. For a rotating turbine blade, however, the channel orientation (β, the angle between the jet direction and the rotating plane) could play an important role in influencing the flow field and heat transfer. Therefore, in this work, the effects of channel orientation (from 90° to 180°) on heat transfer in a jet impingement cooling channel are experimentally investigated. Furthermore, the investigations are conducted under an isothermal boundary condition. Both the jet-to-target surface distance and jet-to-jet spacing are three times the jet hole diameter. The jet Reynolds number is 5,000, and the maximum jet rotation number reaches 0.24. The results show that the rotation-induced variations of heat transfer are different in each channel orientation. In the cases of 90°≤β≤135°, a vortex generated in the low-radius region of the supply channel changes the mass-flowrate distribution in each jet hole. Therefore, the heat transfer in the low-radius region decreases with the rotation number, whereas the heat transfer in the high-radius region increases, indicating that a larger temperature gradient in the radial direction could appear in the turbine blade's leading edge. When 135°<β≤180°; however, the heat transfer of the entire stagnant zone decreases with the rotation number. The rotation-induced jet deflection is the primary factor that weakens the heat transfer, and jets cannot reach the target surface at high rotation numbers. For the downstream regions, however, the heat transfer is enhanced by 50%-80% in every channel orientation because the dead zone is broken by the rotation-induced secondary flow in the impingement channel.

Keywords: heat transfer, jet impingement cooling, channel orientation, high rotation number, isothermal boundary

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Authors: Gesti Prastiti, Maylina Adani, Yuyun darma A. N., M. Khilmi F., Yunita Wahyu Pratiwi

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Combination therapy may allow interaction on two drugs or more that can give adverse effects on patients. Simvastatin is a drug of antihyperlipidemia it can interact with drugs which work on cytochrome P450 CYP3A4 because it can interfere the performance of simvastatin. Flavonoid found in plants can inhibit the cytochrome P450 CYP3A4 if taken with simvastatin and can increase simvastatin levels in the body and increases the potential side effects of simvastatin such as myopati and rhabdomyolysis. Green tea leaves and mint are herbal medicine which has the effect of antihiperlipidemia. This study aims to determine the potential interaction of simvastatin with herbal drinks (green tea leaves and mint). This research method are experimental post-test only control design. Test subjects were divided into 5 groups: normal group, negative control group, simvastatin group, a combination of green tea group and the combination group mint leaves. The study was conducted over 32 days and total cholesterol levels were analyzed by enzymatic colorimetric test method. Results of this study is the obtainment of average value of total cholesterol in each group, the normal group (65.92 mg/dL), the negative control group the average total cholesterol test in the normal group was (69.86 mg/dL), simvastatin group (58.96 mg/dL), the combination of green tea group (58.96 mg/dL), and the combination of mint leaves (63.68 mg/dL). The conclusion is between simvastatin combination therapy with herbal drinks have the potential for pharmacodynamic interactions with a synergistic effect, antagonist, and a powerful additive, so the combination therapy are no more effective than a single administration of simvastatin therapy.

Keywords: hyperlipidemia, simvastatin, herbal drinks, green tea leaves, mint leaves, drug interactions

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Authors: Debra L. Stanley, Gabriela Wasileski

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Offenders face many challenges as they transition from being incarcerated to the community, ranging from housing and employment needs to long standing problems with addictions and mental health issues. A lack of appropriate behavioral health services in the more remote parts of the United States has led to a significant illegal substance abuse problem, housing instability, and unaddressed mental health and trauma issues. High rates of poverty and unemployment exacerbate the growing behavioral health issues, drug overdoses, co-occurring disorders, and crime that are so prevalent across rural communities. This study examines the challenges of rural jail reentry faced by offenders in a treatment capacity. The client-centered evidence-based program is uniquely designed to provide continuity of care that focuses on issues which affect rural communities. Prior to release from jail, individuals go through comprehensive assessment screenings to measure mental health and substance use disorder as well as trauma and prior crime victimization histories; the assessments help to target client-specific services. The quasi-experimental research design tracks clients throughout their recovery and reintegration into the community. Individuals in a rural program often do not have the benefit of easy access or peer mentoring that is so often found in urban recovery programs. Therefore, much of the support is provided through telehealth and e-services. The goal of this study is to explore the nature of rural reentry programs and measures of recidivism, drug overdoses, and other behavioral health needs and successful reentry to include stable housing and employment.

Keywords: jail reentry, rehabilitation, behavioral health, drug abuse, recidivism

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Authors: Sunil Kumar, Rajesh Sharma

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Toxic epidermal necrolysis, pruritis, rashes, lichen planus like eruption, hyper pigmentation of skin are rare toxic effects of choloroquine used over a long time. Skin and mucus membrane hyper pigmentation is generally of a bluish black or grayish color and irreversible after discontinuation of the drug. According to Ayurveda, Dushivisha is the name given to any poisonous substance which is not fully endowed with the qualities of poison by nature (i.e. it acts as an impoverished or weak poison) and because of its mild potency, it remains in the body for many years causing various symptoms, one among them being discoloration of skin.The objective of this case report is to investigate the effect of Ayurvedic management of chloroquine induced hyper-pigmentation on the line of treatment of Dushivisha. Case Report: A 26-year-old female was suffering from hyper-pigmentation of the skin over the neck, forehead, temporo-mandibular joints, upper back and posterior aspect of both the arms since 8 years had history of taking Chloroquine came to Out Patient Department of National Institute of Ayurveda, Jaipur, India in Jan. 2015. The routine investigations (CBC, ESR, Eosinophil count) were within normal limits. Punch biopsy skin studied for histopathology under hematoxylin and eosin staining showed epidermis with hyper-pigmentation of the basal layer. In the papillary dermis as well as deep dermis there were scattered melanophages along with infiltration by mononuclear cells. There was no deposition of amyloid-like substances. These histopathological findings were suggestive of Chloroquine induced hyper-pigmentation. The case was treated on the line of treatment of Dushivisha and was given Vamana and Virechana (therapeutic emesis and purgation) every six months followed by Snehana karma (oleation therapy) with Panchatikta Ghrit and Swedana (sudation). Arogyavardhini Vati -1 g, Dushivishari Vati 500 mg, Mahamanjisthadi Quath 20 ml were given twelve hourly and Aragwadhadi Quath 25 ml at bed time orally. The patient started showing lightening of the pigments after six months and almost complete remission after 12 months of the treatment. Conclusion: This patient presented with the Dushivisha effect of Chloroquineandwas administered two relevant procedures from Panchakarma viz. Vamana and Virechana. Both Vamana and Virechanakarma here referred to Shodhana karma (purification procedures) eliminates accumulated toxins from the body. In this process, oleation dislodge the toxins from the tissues and sudation helps to bring them to the alimentary tract. The line of treatment did not target direct hypo pigmentary effects; rather aimed to eliminate the Dushivisha. This gave promising results in this condition.

Keywords: Ayurveda, chloroquine, Dushivisha, hyper-pigmentation

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Authors: Hasan Afarnegan, Ali Shahraki, Jafar Shahraki

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Paraquat is widely used as a strong nitrogen-based herbicide for controlling of weeds in agriculture. This poison is extremely toxic for humans which induces several – organ failure by accumulation in cells and many instances of death occurred due to its poisoning. Paraquat metabolized primarily in the liver. The purpose of this study was to assess the effects of aquatic extract of levisticum officinale on oxidative status and biochemical factors in hepatocytes exposed to paraquat. Our results determined that hepatocytes destruction induced by paraquat is mediated by reactive oxygen species (ROS) production, lipid peroxidation and decrease of mitochondrial membrane potential were significantly (P<0.05) prevented by aquatic extract of Levisicum officinale (100, 200 and 300 µg/ml). These effects of paraquat also prevented via antioxidants and ROS scavengers (α-tocopherol, DMSO, manitol), mitochondrial permeability transition (MPT) pore sealing compound (carnitine).MPT pore sealing compound inhibited the hepatotoxicity, indicating that paraquat induced cell death via mithochondrial pathway. Pretreatment of hepatocytes with aquatic extracts of Levisticum officinale, antioxidants and ROS scavengers also blocked hepatic cell death caused by paraquat, suggesting that oxidative stress may be directly induced decline of mithochondrial membrane potential. In conclusion, paraquat hepatotoxicity can be attributed to oxidative stress and continued by mithochondrial membrane potential disruption. Levisticum officinale aquatic extract, presumably due to its strong antoxidant properties, could protect the destructive effects of paraquat on rat hepatocytes.

Keywords: hepatocyte protection, levisticum officinale, oxidative stress, paraquat

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia AbdulMajid, Maryam Zahedifard

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Colon cancer is one of the most prevalent cancers in the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. New schiff based compounds are reported to exhibit a wide spectrum of biological activities of therapeutic importance. To evaluate inhibitory properties of CdCl2(C14H21N3O2) complex on colonic aberrant crypt foci, five groups of 7-week-old male rats were used. Control group was fed with 10% Tween 20 once a day, cancer control group was intra-peritoneally injected with 15 mg/kg Azoxymethan, drug control group was injected with 15 mg/kg azoxymethan and 5-Flourouracil, experimental groups were fed with 2.5 and 5 mg/kg CdCl2(C14H21N3O2) compound each once a day. Administration of compound were found to be effectively chemoprotective. Andrographolide suppressed total colonic ACF formation up to 72% to 74%, respectively, when compared with control group. The results also showed a significant increase in glutathione peroxidase, superoxide dismutase, catalase activities and a decrease in malondialdehyde level. Immunohistochemical staining demonstrated down-regulation of PCNA protein. According to the Western blot comparison analysis, COX-2 and Bcl2 is up-regulated whilst the Bax is down-regulated. according to these data, this compound plays promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, Schiff based compound, aberrant crypt foci (ACF), immunohistochemical staining

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: M. Yoneda

Abstract:

In this paper, a lateral walking design force per person is proposed and compared with Imperial College test results. Numerical simulations considering the proposed walking design force which is incorporated into the neural-oscillator model are carried out placing much emphasis on the synchronization (the lock-in phenomenon) for a pedestrian bridge model with the span length of 50 m. Numerical analyses are also conducted for an existing pedestrian suspension bridge. As compared with full scale measurements for this suspension bridge, it is confirmed that the analytical method based on the neural-oscillator model might be one of the useful ways to explain the synchronization (the lock-in phenomenon) of pedestrians being on the bridge.

Keywords: pedestrian bridge, human-induced lateral vibration, neural-oscillator, full scale measurement, dynamic response analysis

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

Abstract:

Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli

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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing

Procedia PDF Downloads 299

Authors: Manal M. Shehata, Kawther M. Abdel-Hamid, Nashwa A. Mohamed, Marwa H. Bakr, Maged S. Mahmoud, Hala M. Elbadre

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Introduction: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. Curcumin, is a dietary spice with antioxidant activity. Aim of work: The present study was undertaken to investigate the therapeutic potential of curcumin, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Material and Methods: Fifty adult male healthy albino rats were included in the present study.They were divided into two groups: Group І: (control group) included 10 rats. Group П: (diabetic group): included 40 rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). Group II will be further subdivided into four groups (10 rats for each): Group II-a (diabetic control). Group II-b: rats were received single intraperitoneal injection of bone marrow suspension (un-fractionated bone marrow cells) prepared from rats of the same family. Group II-c: rats were treated with curcumin orally by gastric intubation for 6 weeks. Group II-d: rats were received a combination of single bone marrow transplantation and curcumin for 6 weeks. After 6 weeks, blood glucose, insulin levels were measured and the pancreas from all rats were processed for Histological, Immunohistochemical and morphometric examination. Results: Diabetic group, showed progressive histological changes in the pancreatic islets. Treatment with either curcumin or bone marrow transplantation improved the structure of the islets and reversed streptozotocin-induced hyperglycemia and hypoinsulinemia. Combination of curcumin and bone marrow transplantation elicited more profound alleviation of streptozotocin-induced changes including islet regeneration and insulin secretion. Conclusion: The use of natural antioxidants combined with bone marrow transplantation to induce pancreatic regeneration is a promising strategy in the management of diabetes.

Keywords: diabtes, panceatic islets, bone marrow transplantation, curcumin

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Authors: Pooyan Changizian, Zhongwen Yao

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The purpose of current study is to make an excellent correlation between mechanical properties and microstructures of ion irradiated X-750 Ni-based superalloy. Towards this end, two different irradiation procedures were carried out, including single Ni ion irradiation and pre-helium implantation with subsequent Ni ion irradiation. Nano-indentation technique was employed to evaluate the mechanical properties of irradiated material. The nano-hardness measurements depict highly different results for two irradiation procedures. Single ion irradiated X-750 shows softening behavior; however, pre-helium implanted specimens present significant hardening compared to the un-irradiated material. Cross-section TEM examination demonstrates that softening is attributed to the γ׳-precipitate instability (disordering/dissolution) which overcomes the hardening effect of irradiation-induced defects. In contrast, the presence of cavities or helium bubbles is probably the main cause for irradiation-induced hardening of helium implanted samples.

Keywords: Inconel X-750, nanoindentation, helium bubbles, defects

Procedia PDF Downloads 217

Authors: J. Desbrieres, M. Popa, C. Peptu, S. Bacaita

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Because of their favorable properties (non-toxicity, biodegradability, mucoadhesivity etc.), polysaccharides were studied as biomaterials and as pharmaceutical excipients in drug formulations. These formulations may be produced in a wide variety of forms including hydrogels, hydrogel based particles (or capsules), films etc. In these formulations, the polysaccharide based materials are able to provide local delivery of loaded therapeutic agents but their delivery can be rapid and not easily time-controllable due to, particularly, the burst effect. This leads to a loss in drug efficiency and lifetime. To overcome the consequences of burst effect, systems involving liposomes incorporated into polysaccharide hydrogels may appear as a promising material in tissue engineering, regenerative medicine and drug loading systems. Liposomes are spherical self-closed structures, composed of curved lipid bilayers, which enclose part of the surrounding solvent into their structure. The simplicity of production, their biocompatibility, the size and similar composition of cells, the possibility of size adjustment for specific applications, the ability of hydrophilic or/and hydrophobic drug loading make them a revolutionary tool in nanomedicine and biomedical domain. Drug delivery systems were developed as hydrogels containing chitosan or carboxymethylcellulose (CMC) as polysaccharides and gelatin (GEL) as polypeptide, and phosphatidylcholine or phosphatidylcholine/cholesterol liposomes able to accurately control this delivery, without any burst effect. Hydrogels based on CMC were covalently crosslinked using glutaraldehyde, whereas chitosan based hydrogels were double crosslinked (ionically using sodium tripolyphosphate or sodium sulphate and covalently using glutaraldehyde). It has been proven that the liposome integrity is highly protected during the crosslinking procedure for the formation of the film network. Calcein was used as model active matter for delivery experiments. Multi-Lamellar vesicles (MLV) and Small Uni-Lamellar Vesicles (SUV) were prepared and compared. The liposomes are well distributed throughout the whole area of the film, and the vesicle distribution is equivalent (for both types of liposomes evaluated) on the film surface as well as deeper (100 microns) in the film matrix. An obvious decrease of the burst effect was observed in presence of liposomes as well as a uniform increase of calcein release that continues even at large time scales. Liposomes act as an extra barrier for calcein release. Systems containing MLVs release higher amounts of calcein compared to systems containing SUVs, although these liposomes are more stable in the matrix and diffuse with difficulty. This difference comes from the higher quantity of calcein present within the MLV in relation with their size. Modeling of release kinetics curves was performed and the release of hydrophilic drugs may be described by a multi-scale mechanism characterized by four distinct phases, each of them being characterized by a different kinetics model (Higuchi equation, Korsmeyer-Peppas model etc.). Knowledge of such models will be a very interesting tool for designing new formulations for tissue engineering, regenerative medicine and drug delivery systems.

Keywords: controlled and delayed release, hydrogels, liposomes, polysaccharides

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Authors: Larissa M. Vargas, Julia M. Sacchi, Renata O. Pereira, Lucas S. Asano, Iara C. Araújo, Patricia Fiorino, Vera Farah

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The aim of this study was to evaluate the occurrence of subclinical organ injuries induced by high-fat diet. Male wistar rats (n=5/group) were divided in control diet group (CD), commercial rat chow, and hyperlipidic diet (30% lipids) group (HD) administrated during 8 weeks, starting after weaning. All the procedures followed the rules of the Committee of Research and Ethics of the Mackenzie University (CEUA Nº 077/03/2011). At the end of protocol the animals were euthanized by anesthesia overload and the left kidney was removed. Intrarenal lipid deposition was evaluated by histological analyses with oilred. Kidney slices were stained with picrosirius red to evaluate the area of the Bowman's capsule (AB) and space (SB), and glomerular tuft area (GT). The renal expression of sterol regulatory element–binding protein (SREBP-2) was performed by Western Blotting. Creatinine concentration (serum and urine) and lipid profile were determined by colorimetric kit (Labtest). At the end of the protocol there was no differences in body weight between the groups, however the HD showed a marked increase in lipid deposits, glomeruli and tubules, and biochemical analysis for cholesterol and triglycerides. Moreover, in the kidney, the high-fat diet induced a reduction in the AB (13%), GT (18%) and SB (17%) associated with a reduction in glomerular filtration rate (creatinine clearance). The renal SRBP2 expression was increased in HD group. These data suggests that consumption of high-fat diet starting in childhood is associated with subclinical renal damage and function.

Keywords: high-fat diet, kidney, intrarenal lipid deposition, SRBP2

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Authors: Pedro J. Rolim-Neto, Leslie R. M. Ferraz, Fabiana L. A. Santos, Pablo A. Ferreira, Ricardo T. L. Maia-Jr., Magaly A. M. Lyra, Danilo A F. Fonte, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim

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Initially developed as an antimalarial agent, hydroxychloroquine (HCQ) sulfate is often used as a slow-acting antirheumatic drug in the treatment of disorders of connective tissue. The United States Pharmacopeia (USP) 37 provides a reversed-phase HPLC method for quantification of HCQ. However, this method was not reproducible, producing asymmetric peaks in a long analysis time. The asymmetry of the peak may cause an incorrect calculation of the concentration of the sample. Furthermore, the analysis time is unacceptable, especially regarding the routine of a pharmaceutical industry. The aiming of this study was to develop a fast, easy and efficient method for quantification of HCQ sulfate by High Performance Liquid Chromatography (HPLC) based on the Quality by Design (QbD) methodology. This method was optimized in terms of peak symmetry using the surface area graphic as the Design of Experiments (DoE) and the tailing factor (TF) as an indicator to the Design Space (DS). The reference method used was that described at USP 37 to the quantification of the drug. For the optimized method, was proposed a 33 factorial design, based on the QbD concepts. The DS was created with the TF (in a range between 0.98 and 1.2) in order to demonstrate the ideal analytical conditions. Changes were made in the composition of the USP mobile-phase (USP-MP): USP-MP: Methanol (90:10 v/v, 80:20 v/v and 70:30 v/v), in the flow (0.8, 1.0 and 1.2 mL) and in the oven temperature (30, 35, and 40ºC). The USP method allowed the quantification of drug in a long time (40-50 minutes). In addition, the method uses a high flow rate (1,5 mL.min-1) which increases the consumption of expensive solvents HPLC grade. The main problem observed was the TF value (1,8) that would be accepted if the drug was not a racemic mixture, since the co-elution of the isomers can become an unreliable peak integration. Therefore, the optimization was suggested in order to reduce the analysis time, aiming a better peak resolution and TF. For the optimization method, by the analysis of the surface-response plot it was possible to confirm the ideal setting analytical condition: 45 °C, 0,8 mL.min-1 and 80:20 USP-MP: Methanol. The optimized HPLC method enabled the quantification of HCQ sulfate, with a peak of high resolution, showing a TF value of 1,17. This promotes good co-elution of isomers of the HCQ, ensuring an accurate quantification of the raw material as racemic mixture. This method also proved to be 18 times faster, approximately, compared to the reference method, using a lower flow rate, reducing even more the consumption of the solvents and, consequently, the analysis cost. Thus, an analytical method for the quantification of HCQ sulfate was optimized using QbD methodology. This method proved to be faster and more efficient than the USP method, regarding the retention time and, especially, the peak resolution. The higher resolution in the chromatogram peaks supports the implementation of the method for quantification of the drug as racemic mixture, not requiring the separation of isomers.

Keywords: analytical method, hydroxychloroquine sulfate, quality by design, surface area graphic

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Authors: Kotchamon Yodkhum, Thawatchai Phaechamud

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Hydrophobic chitosan-based materials have been developed as controlled drug delivery system. This study was aimed to prepare and evaluate chitosan-aluminum monostearate composite dispersion (CLA) as fabricating liquid for construct a hydrophobic, controlled-release solid drug delivery matrix. This work was attempted to blend hydrophobic substance, aluminum monostearate (AMS), with chitosan in acidic aqueous medium without using any surfactants or grafting reaction, and high temperature during mixing that are normally performed when preparing hydrophobic chitosan system. Lactic acid solution (2%w/v) was employed as chitosan solvent. CLA dispersion was prepared by dispersing different amounts of AMS (1-20% w/w) in chitosan solution (4% w/w) with continuous agitation using magnetic stirrer for 24 h. Effect of AMS amount on physicochemical properties of the dispersion such as viscosity, rheology and particle size was evaluated. Morphology of chitosan-AMS complex (dispersant) was observed under inverted microscope and atomic force microscope. Stability of CLA dispersions was evaluated after preparation within 48 h. CLA dispersions containing AMS less than 5 % w/w exhibited rheological behavior as Newtonian while that containing higher AMS amount exhibited as pseudoplastic. Particle size of the dispersant was significantly smaller when AMS amount was increased up to 5% w/w and was not different between the higher AMS amount system. Morphology of the dispersant under inverted microscope displayed irregular shape and their size exhibited the same trend with particle size measurement. Observation of the dispersion stability revealed that phase separation occurred faster in the system containing higher AMS amount which indicated lower stability of the system. However, the dispersions were homogeneous and stable more than 12 hours after preparation that enough for fabrication process. The prepared dispersions had ability to be fabricated as a porous matrix via lyophilization technique.

Keywords: chitosan, aluminum monostearate, dispersion, controlled-release

Procedia PDF Downloads 390

Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

Procedia PDF Downloads 254