Anticancer Drug Cyclophosphamide Research Articles

Study the effect of a new nikel (II) Complex and anticancer drug (cp) on Liver enzyme activity (GPT,GOT) and Creatinine level in Kidney of femal mice

This study involved the effect of anew nickel (II) complexs with formla [NiL2(H2O)2].2.5ETOH where L=Bis[5-(p-nitrophenyL)-4-phenyL-1,2,4-traizole-3-dithocarbamato hydrazide] diaqua. nickel(II). Ethanol(2.5).and anti-cancer drug cyclophosphamide on specific actifity of two Liver enzymes (GOT,GPT) in the (Liver,kidney) tissues and on the creatinine Level in the kidney byUtilizing an invivosystem in femalmice.The result showed that inhibition in the activity of GPT and GOT enzymes in theLiver and in both nickel (II) complex and cyclophosphamide drug (CP) . mice weretreated with three doses (90,180,320) µg/mouse for three days for each group.The Liver show's the highest rate of GPT inhibition was about 97.43% at180µg/mouse regarding the kidney the inhibition rate was about 98.63% at 180µg/mouse .The maximum inhibition of GOT enzame in the Liver was about 77. 48% ataconcentration 180µg/mouse and the inhbition rate of GOT enzyme in the kidney was about 97.87% at aconcentration 320µg/mouse.The result showed the effect of nickel (II) complex on the creatinine Level in the kidney ,The maximum activation was about 99.45% at 320µg/mouse.

Protective effects of common anthocyanidins against genotoxic damage induced by chemotherapeutic drugs in mice.

Experiments were performed to assess in mice the inhibitory effects of the anthocyanidins cyanidin, delphinidin, malvidin, and pelargonidin on genotoxic damage induced by the anticancer drugs cyclophosphamide, procarbazine, and cisplatin. Each anthocyanidin was administered 30 min before injecting the drug, and genotoxicity was assessed by measuring micronucleated polychromatic erythrocytes in bone marrow cells. In addition, we monitored the effect of anthocyanidins on apoptosis induced by cyclophosphamide and procarbazine. The results showed significant protective effects of cyanidin, delphinidin, malvidin, and pelargonidin against DNA damage induced by cyclophosphamide. With delphinidin and malvidin, a biphasic dose-response was observed for protection against cyclophosphamide. Dose-related reduction of genotoxicity was observed with pelargonidin against procarbazine. However with cyanidin, the medium dose of 2 mg/kg showed maximum protection against procarbazine. Cyanidin and pelargonidin significantly reduced the chromosomal damage induced by cisplatin. Furthermore, pre-treatment with these anthocyanidins reduced the level of apoptosis induced by cyclophosphamide and procarbazine. In conclusion, this study shows that anthocyanidins can reduce the efficacy of anticancer drugs for inducing DNA damage and apoptosis.

Antimutagenicity and phytoconstituents of Egyptian Plantago albicans L.

ObjectiveTo evaluate the safety and the possible antimutagenic effect of the defatted aqueous ethanol extract and polysaccharide extract of Plantago albicans L. areal parts on the genotoxicity of the anticancer drug cyclophosphamide and to investigate the chemical constituents of these extracts. MethodsTwo doses of each extract (10 and 15 mg/kg body weight) were administered orally to albino mice 7 d prior to treatment of cyclophosphamide (20 mg/kg body weight, i.p). Chromosomal aberration analysis and micronucleus test were performed. Phytochemical investigation of defatted aqueous ethanol extract was carried out through chromatographic tools, chemical and physical analysis to know the active constituents of these extracts. ResultsGroups of mice administered with defatted aqueous ethanol extract and polysaccharide extract prior to cyclophosphamide treatment showed statistically significant reduction in the percentage of chromosomal aberrations and micronuclei in bone marrow cells in a dose-dependent manner. Defatted aqueous ethanol extract gave more effective protection in comparison with polysaccharide extract. Phytochemical investigation of defatted aqueous ethanol extract allowed isolation of gallic acid, methylgallate, tri, tetra, penta-galloyl-β-glucopyranoside, kaempferol-3-O-β-sophro pyranoside, quercetin-3-O-β-glucopyranoside-7-O-α-rhamnpyranoside, kaempferol and quercetin, for the first time from this species. ConclusionsThe results of the present work demonstrated that Plantago albicans phytoconstituents play a protective role against genotoxicity of the drug cyclophosphamide.

English

English

Determination of six chemotherapeutic agents in municipal wastewater using online solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry

Due to the increased consumption of chemotherapeutic agents, their high toxicity, carcinogenicity, their occurrence in the aquatic environment must be properly evaluated. An analytical method based on online solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry was developed and validated. A 1mL injection volume was used to quantify six of the most widely used cytotoxic drugs (cyclophosphamide, gemcitabine, ifosfamide, methotrexate, irinotecan and epirubicin) in municipal wastewater. The method was validated using standard additions. The validation results in wastewater influent had coefficients of determination (R2) between 0.983 and 0.998 and intra-day precision ranging from 7 to 13% (expressed as relative standard deviation %RSD), and from 9 to 23% for inter-day precision. Limits of detection ranged from 4 to 20ngL−1 while recovery values were greater than 70% except for gemcitabine, which is the most hydrophilic compound in the selected group and had a recovery of 47%. Matrix effects were interpreted by signal suppression and ranged from 55 to 118% with cyclophosphamide having the highest value. Two of the target anticancer drugs (cyclophosphamide and methotrexate) were detected and quantified in wastewater (effluent and influent) and ranged from 13 to 60ngL−1. The proposed method thus allows proper monitoring of potential environmental releases of chemotherapy agents.

발계(Smilax china L.) 열수 및 에탄올 추출물의 항산화 및 항암활성

The biological activities of Smilax china L. rhizome (SCR), hot water (SCRW) and 70% ethanol extract (SCRE) were analyzed. The total phenolic contents of SCRW and SCRE were 51.7 and 100.5 mg/g, respectively. The measured flavonoid content of SCRW (61.7 μg/g) was almost double that of SCRE (31.7 μg/g). SCRE (IC50=42.4 μg/mL) exhibited stronger antioxidant activity in the DPPH system than the positive control α-tocopherol (71.3 μg/mL) or butylated hydroxy anisole (53.8 μg/mL) did. SCRE (IC50=50.3 μg/mL) also showed stronger ABTS radical scavenging activity, as did α-tocopherol (67.1 μg/mL). The SOD-like activity and Tyrosinase inhibition activity of SCRW and SCRE showed almost the same pattern. The best SOD-like activity and tyrosinase inhibition activity were measured as 24.9% and 20.3% in SCRW at 1,000 μg/mL, respectively. The cytotoxic effects of the SCR extracts were analyzed via MTT assay on human cancer and normal cells. SCRW and SCRE did not show cytotoxicity up to the concentration of 1,000 μg/mL against the normal human cell line HEK293. Against human breast cancer cells (MCF-7), SCRW inhibited MCF-7 growth (by 27.6%) better than the anticancer drug cyclophosphamide (15.5%) at 1,000 μg/mL. SCRE (1,000 μg/mL) inhibited the growth of human lung cancer cells A549 (37.6%) and human stomach cancer cells AGS (53.6%) more effective than did SCRW (21.0% and 35.4%) or CPA (22.2% and 31.7%). These results suggest the potential use of SCRE and SCRW as an excellent antioxidant and antiproliferative substance, respectively.

Cell chip with a thiolated chitosan self-assembled monolayer to detect the effects of anticancer drugs on breast normal and cancer cells

Cell-based chips are an effective in vitro analysis tool; however, the sensitivity of the cell chip to biomaterials is high, which is crucial for immobilizing cells on the electrode surface without conductivity. In this study, we report on a cell chip with a thiolated chitosan monolayer that was easy to fabricate, highly adhesive to cells, and enhanced electrochemical signals. Thiolated chitosan containing thiol groups was synthesized and self-assembled on a gold electrode to immobilize cells, and showed superior electrochemical performance to that of poly-l-lysine and collagen. Cyclic voltammetry (CV) was performed to distinguish the redox characteristics of normal (HMEC) and breast cancer cells (MCF-7); then, two anticancer drugs (doxorubicin and cyclophosphamide) were added to the cell cultures to analyze their effects on the redox environment of normal and cancer cells derived from the same origin. As a result, the CV cathode peaks decreased differently with respect to the cell line (normal and cancer) and anticancer drug, which was validated by a conventional MTT viability assay. Hence, the proposed cell chip with a thiolated chitosan modified layer could be used in various fields, including discriminating normal from cancer cells, to evaluating the efficiency of newly developed drugs, and to assessing cytotoxicity of various chemicals.

The influence of the anticancer drug cyclophosphamide on fertilization and embryo growth in a mouse model

Currently, unfertilized oocytes from patients undergoing chemotherapy are frozen for future use. Therefore, the object of this study was to evaluate the influence of an anticancer drug on fertilization and embryo growth in mice.

Tamoxifen in Trimodal Therapy with Cytotoxic Drugs and Hyperthermia in Vivo Significantly Enhance Therapeutic Efficacy against B16-F10 Melanoma

The aim of the study was to investigate whether use of the antiestrogen tamoxifen and heat treatment in combined therapy with the well-known anticancer drugs cisplatin, dacarbazine and cyclophosphamide enhances their therapeutic efficacy on mouse B16-F10 melanoma in vivo. The results of systemic melanoma therapy have been mostly disappointing. Therefore, there is still a great need for strategies that can improve existing chemotherapy options. The tumor model for the investigation of antitumor activity was a mouse B16-F10 melanoma transplanted into the footpad of C57BL/6 Zgr/Hr mice. Drugs were given intraperitoneally 15 min before the application of local hyperthermia, and tumor growth and mouse survival were followed. Hyperthermia alone determined a significant delay of tumor growth, but mouse survival was not affected. In bimodal combinations with hyperthermia, all the tested antitumor drugs significantly increased both tumor growth delay and mouse survival. Tamoxifen alone did not show any inhibitory effect on B16-F10 melanoma in vivo. However, in the trimodal therapy with a particular drug and hyperthermia, it potentiated the inhibitory effects of the respective bimodal treatments, especially that of cyclophosphamide and hyperthermia. Our results obtained on the mouse B16-F10 melanoma in vivo confirmed the enhanced therapeutic efficacy of the trimodal therapy tamoxifen, hyperthermia and anticancer drug combinations in melanoma treatment. Further studies should optimize the heat-drug time scheduling and drug doses that will result in the best possible therapeutic achievement for these trimodal therapy options.

ChemInform Abstract: 1‐Hydroxy‐8‐methyl‐1,4,8‐triazaspiro[4.5]decan‐2‐one and Its (.+‐.)‐3‐Methyl Homologue: Regioselective Synthesis and in vivo Evaluation as Adjuvants in Leukemia Chemotherapy.

AbstractThe condensation reaction of glycine and alanine hydroxamic acids with piperidone (II) regioselectively affords the title spiro compounds (III), which are capable of enhancing sensitivity of P388 and L1210 leukemias in mice models to the known anticancer drugs cisplatin and cyclophosphamide.

1-Hydroxy-8-methyl-1,4,8-triazaspiro[4.5]decan-2-one and its (±)-3-methyl homologue: regioselective synthesis and in vivo evaluation as adjuvants in leukemia chemotherapy

Condensation of glycine and dl-alanine hydroxamic acids with 1-methyl-4-piperidone regioselectively gave the corresponding titled spiro piperidine hydroxyimidazolidinones capable of enhancing sensitivity of P388 and L1210 leukemias in mice models to the known anticancer drugs cisplatin and cyclophosphamide.

Analysis of Anticancer Drugs in Sewage Water By Selective SPE and UPLC-ESI-MS-MS

A trace analytical procedure was developed to assay the anticancer drugs methotrexate, azathioprine, doxorubicin, doxorubicinol, vincristine, ifosfamide, cyclophosphamide, etoposide, and procarbazine in water samples from sewage treatment plants. After concentration and purification using Oasis HLB solid-phase extraction cartridges and Oasis WAX cartridges, the analytes were separated using ultra-high performance liquid chromatography coupled with the electrospray ionization tandem mass spectrometry operating in the positive ion mode. The method showed good precision and accuracy. Recoveries of all analytes were in the range of 45.3-108.9% with relative standard deviations between 2.4-24.5%. The limits of detection for influent and effluent sewage water were in the range of 0.6-7.0 ng/L and 0.5-3.5 ng/L, respectively. It is expected that this method will be applied to investigate the environmental occurrence of anticancer drugs in sewage water.

Liver transplantation for colorectal liver metastases: revisiting the concept

Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1- and 5-year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5-year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.

Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide

Constituents of the Nigella sativa seed are reported to possess potent antioxidant effects. Treatment with anticancer drugs such as cyclophosphamide (CTX) is associated with significant toxicity due to over-production of reactive oxygen species, resulting in increased levels of oxidative stress. The aim of this study is to test whether or not N. sativa L oil (NSO) or its active ingredient, thymoquinone (TQ), can reduce CTX-induced toxicity. Male albino rats were treated with intraperitoneal administration of phosphate buffered saline (PBS) or 200 mg/Kg CTX followed by intragastric administration of NSO or TQ on alternate days for 12 days. Administration of NSO and TQ was initiated 6 h before or after CTX injection. Twenty-four hours after the last NSO and TQ treatment, blood and liver were harvested to analyse toxicity-related parameters. Treatment with CTX induced significant toxicity as shown by decrease in haemoglobin concentration and increases in blood sugar levels, activities of liver enzymes, bilirubin, urea, creatinine, lipids (triglyceride, cholesterol and low-density lipoprotein (LDL)-cholesterol) and lipid peroxidation in the liver. Treatment with NSO or TQ induced significant reduction in overall toxicity. The antitoxic effects of NSO and TQ were associated with induction of antioxidant mechanisms. These results suggest that administration of NSO or TQ can lower CTX-induced toxicity as shown by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimise the toxic effects of treatment with anticancer drugs.

Seleno l-Methionine Acts on Cyclophosphamide-Induced Kidney Toxicity

The anticancer drug cyclophosphamide (CP) has nephrotoxic effects besides its urotoxicity, which both in turn limit its clinical utility. The nephrotoxicity of CP is less common compared to its urotoxicity, and not much importance has been given for the study of mechanism of CP-induced nephrotoxicity so far. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the kidney injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the nephrotoxicity of CP and the possible protective effects of seleno L-methionine (SLM) on rat kidneys were investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats each. The control group received saline, and other rats were injected with CP (100 mg/kg), SLM (0.5 or 1 mg/kg), or CP + SLM intraperitoneally. Malondialdehyde (MDA) and glutathione (GSH) levels in kidney homogenates of rats were measured, and kidney tissues were examined under the microscope. CP-treated rats showed a depletion of renal GSH levels (28% of control), while CP + SLM-injected rats had GSH values close to the control group. MDA levels increased 36% of control following CP administration, which were significantly decreased after SLM treatment. Furthermore, these biochemical results were supported by microscopical observations. In conclusion, the present study not only points to the therapeutic potential of SLM in CP-induced kidney toxicity but also indicates a significant role for ROS and their relation to kidney dysfunction.

Simple route to ferrocenylalkyl nucleobases. Antitumor activity in vivo

AbstractFerrocenylalkyl nucleobases (1–14) were prepared via the reaction of the α‐(hydroxy)alkyl ferrocenes FcCHR(OH) (Fc = ferrocenyl; R = H, Me, Et, Ph) with thymine, cytosine, iodo‐cytosine and adenine in DMSO at 100 °C, yields being 50–80%. The antitumor activities of ferrocenylmethyl thymine (1) against solid tumor models, carcinoma 755 (Ca755) and Lewis lung carcinoma (LLC) were studied in vivo. Therapeutic synergism of antitumor activity against LLC was demonstrated in the case of combined application of compound 1 with anticancer drug cyclophosphamide. Copyright © 2009 John Wiley & Sons, Ltd.

Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: A study in mice

Astaxanthin, a natural and nutritional red carotenoid pigment, is used as a dietary supplement. The intention of the present study was to investigate the beneficial effects of dietary pigment astaxanthin, against cyclophosphamide-induced oxidative stress and DNA damage. The end points of evaluation of the study included: (a) malondialdehyde, glutathione and superoxide dismutase concentration in liver to detect oxidative stress; (b) normal and modified alkaline comet assays (the latter includes lesion-specific enzymes formamidopyrimidine-DNA glycosylase and endonuclease-III) to detect normal and oxidative stress-induced DNA damage by cyclophosphamide in the mouse bone marrow and the peripheral blood lymphocytes. In addition, micronucleus assay and chromosomal aberration test capable of detecting the DNA damage were also carried out in peripheral blood and bone marrow of mice. Cyclophosphamide (100 mg/kg intra-peritoneal) treatment led to significant increase in liver malondialdehyde and decreased the antioxidant enzymes glutathione and superoxide dismutase. Further, cyclophosphamide also significantly increased the DNA damage as observed from normal and modified comet assays as well as micronucleus and chromosomal aberration assay. Pre-treatment with astaxanthin (12.5, 25 and 50 mg/kg/day for 5 days per oral) resulted in the restoration of oxidative stress markers such as malondialdehyde, glutathione and superoxide dismutase in liver. The amelioration of oxidative stress with astaxanthin pre-treatment correlated well with the decreased DNA damage as evident from normal and modified alkaline comet assays of bone marrow cells and peripheral blood lymphocytes. Further astaxanthin pre-treatment also reduced the frequency of chromosomal breakage and micronucleus formation in the mouse bone marrow cells and peripheral blood reticulocytes. It is thus concluded that pre-treatment with astaxanthin attenuates cyclophosphamide-induced oxidative stress and subsequent DNA damage in mice and it can be used as a chemoprotective agent against the toxicity of anticancer drug cyclophosphamide.

Developing of Bacterial Mutagenic Assay System for Detection of Environmental and Food MutagensV – Using Anticancer Drug Cyclophosphamide

G-system composed of three isolates G3 ( Bacillus),G12 ( Arthrobacter )and G27 ( Brevibacterium) was used to detect the mutagenicity of the anticancer drug, cyclophosphamide (CP) under conditions similar to that used for standard mutagen, Nitrosoguanidine (NTG). The CP effected the survival fraction of isolates after treatment for 15 mins using gradual increasing concentrations, but at less extent comparing to NTG. The mutagenic effect of CP was at higher level than that of NTG when using streptomycin as a genetic marker, but the situation was reversed when using rifampicin resistant as a report marker. The latter effect appeared upon recording the mutagen efficiency (ie., number of induced mutants/microgram of mutagen). Measuring the Relative mutability revealed that isolate G12 was highly mutable by both mutagens. The Relative mutational results showed also that isolate G12 is more sensitive, except when recording rifampicin resistance as a genetic marker, and this pattern was similar to NTG.

Developing of Bacterial Mutagenic Assay System for Detection of Environmental and Food MutagensV – Using Anticancer Drug Cyclophosphamide

G-system composed of three isolates G3 ( Bacillus),G12 ( Arthrobacter )and G27 ( Brevibacterium) was used to detect the mutagenicity of the anticancer drug, cyclophosphamide (CP) under conditions similar to that used for standard mutagen, Nitrosoguanidine (NTG). The CP effected the survival fraction of isolates after treatment for 15 mins using gradual increasing concentrations, but at less extent comparing to NTG. The mutagenic effect of CP was at higher level than that of NTG when using streptomycin as a genetic marker, but the situation was reversed when using rifampicin resistant as a report marker. The latter effect appeared upon recording the mutagen efficiency (ie., number of induced mutants/microgram of mutagen). Measuring the Relative mutability revealed that isolate G12 was highly mutable by both mutagens. The Relative mutational results showed also that isolate G12 is more sensitive, except when recording rifampicin resistance as a genetic marker, and this pattern was similar to NTG.

Cell-based chip for the detection of anticancer effect on HeLa cells using cyclic voltammetry

HeLa cells directly immobilized on gold-patterned silicon substrate were used to assess the biological toxicity of anticancer drugs (hydroxyurea and cyclophosphamide). Immobilization of HeLa cells was confirmed by optical microscopy, and cell growth, viability and drug-related toxicity were examined by cyclic voltammetry and potentiometric stripping analysis. The voltammetric behaviors of HeLa cells displayed a quasi-reversible pattern with the peak current exhibiting a linear relationship with cell number. The attached living cells were exposed to different concentrations of hydroxyurea and cyclophosphamide as anticancer drugs, which induced the change of cyclic voltammetry current peak. As the exposed concentration of anticancer drugs was increased, the change of current peak was increased, which indicates the decrease of cell viability. Trypan Blue dyeing was performed to confirm the results of the effect of anticancer drugs on the cell viability which was obtained from cyclic voltammetry assay. The proposed direct cell immobilization method technique can be applied to the fabrication of cell chip for diagnosis, drug detection, and on-site monitoring.