Acute pneumocyte injury, polyadpribose polymerase activity, and pyridine nucleotide levels after in vitro exposure of murine lung slices to cyclophosphamide. The purpose of the present study is to evaluate the chromosomal damages, changes in sister chromatid exchange sces frequencies, in mitotic index mi and in cell cycle kinetics induced by cyclophosphamide cyp encapsulated in liposomes in compare to the free drug in vivo mammalian system. After the mice were sacrificed on day 30 liver and colons were removed, the. Novel insights into the mechanism of cyclophosphamide. Jun 01, 2011 the aim of this article is to elucidate the mechanism by which eicosapentaenoic acid epa acts against cyclophosphamide cp. Cytoxan cyclophosphamide for injection, usp cytoxan tablets. Shortterm comparative study of the cyclophosphamide. The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide cp in mice. It may be concluded that turmeric and myrrh are useful herbal remedies, especially for controlling oxidative damages and genotoxicity induced by lead acetate intoxication. This experimental study was performed to investigate the chemoprotective effects of epo in the liver and pancreas of cpintoxicated mice. Cardiac toxicity is one of the lifethreatening complications of cancer therapy. Therapeutic use of cyclophosphamide and its cytotoxic. Systemic anticancer treatments may exert their own toxic effects or can aggravate adverse effects of other drugs.
Jan 29, 2012 cyclophosphamide cpm, an alkylating agent is used as an immunosuppressant in rheumatoid arthritis and in the treatment of several cancers as well. These data support that enhanced lipid peroxidation in v. Research article the mitigating effect of citrullus. Kinaseindependent inhibition of cyclophosphamideinduced.
Evening primrose oil epo contains several phytoconstituents with potent antioxidant and antiinflammatory activities. Cyclophosphamideinduced nephrotoxicity, genotoxicity, and damage in kidney genomic dna of swiss albino mice. Cyclophosphamide cpm, an alkylating agent is used as an immunosuppressant in rheumatoid arthritis and in the treatment of several cancers as well. Invitro evidence for cyclophosphamideinduced cardiotoxicity. Incorporation of metabolic activation potentiates cyclophosphamide. Pdf protective effect of extracts of teucrium polium and.
Cyclophosphamide is a white crystalline powder with the molecular formula c 7 h 15 cl 2 n 2 o 2 p h 2 o and a molecular weight of 279. Protective effects of boron on cyclophosphamide induced lipid. Protective effects of eicosapentaenoic acid on genotoxicity. Pdf cyclophosphamide is one of the chemotherapeutics for cancer, which is used to treat several types of cancer, however this drug has severe side. Cyclophosphamide cp is commonly used chemotherapeutic and immunosuppressive agent for the treatment of a wide range of neoplastic as well as some utoimmune diseases. Data of 1018 patients 725 women293 men treated with cyc were evaluated in this retrospective study. Chemoprotective effects of zataria multiflora against genotoxicity. Till date, pathophysiology of cyclophosphamide induced cardiotoxicity is not clearly understood. Administration of cyclophosphamide depleted the gsh level in liver. Hepatoprotective effects of zataria multiflora ethanolic. Dads against cyclophosphamide cpinduced testicular toxicity in male rats. Omega3 fatty acids modulate cyclophosphamide induced markers. Cadmiuminduced genotoxicity, cytotoxicity and lipid peroxidation in allium sativum and.
Cyclophosphamide cp is an alkylating agent widely used in cancer chemotherapy. We report a case of cyclophosphamide induced cardiotoxicity in a patient with normal cardiac functions before chemotherapy. Protection by turmeric and myrrh against liver oxidative. Genoprotective effects of origanum vulgare ethanolic extract against. Cyclophosphamide is used to treat cancers and autoimmune diseases. Protective effect of selenium nanoparticle against. The aim of this article is to elucidate the mechanism by which eicosapentaenoic acid epa acts against cyclophosphamide cp.
To assess bladder toxicity of cyclophosphamide cyc and uroprotective effect of mesna in rheumatic diseases. The present study was undertaken to evaluate the natural protective efficacy of methanolic grape seed extract gse against cp induced genotoxicity and histopathologically changes of liver and colon cancer cells in mice. Our results suggest that tq produces a protective mechanism against cp induced genetic damage, and suggest a role of dna strand breaks in the genotoxicity tab. Amelioration of the cyclophosphamide induced genotoxic. Fruit extract against genotoxicity induced by cyclophosphamide in mice bone marrow cells mohammad shokrzadeh, 1, 2 aroona chabra, 3 farshad naghshvar, 4 and amirhossein ahmadi 1. Genotoxicity assessment of saline extract from pilosocereus. Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. Original contribution modulatory effects of total extract of.
This drug also has significant immunosuppressive activity and is used clinically in the treatment of autoimmune diseases and for renal and bone marrow transplantations 1. Cadmiuminduced genotoxicity, cytotoxicity and lipid. It produces highly active carbonium ion, which reacts with the extremely electronrich centers of nucleic acids and proteins. Lipid peroxidation induced by cd is known to be due to the attack of free radicals on the fatty acid component of membrane lipids. However metabolism of cp in the body results into toxic chemical compounds to the liver itself and other nontarget vital organs via oxidative stress, apoptosis induction and finally necrosis. Avocado fruit persea americana mill exhibits chemoprotective potentiality against cyclophosphamide induced genotoxicity in human lymphocyte culture. The length of treatment depends on the types of drugs you are taking, how well your body responds to them, and the type of cancer or condition you have. We previously reported that hesperidin, a citrus bioflavonoid, may have antioxidative activity and can reduce the genotoxicity induced by cp in mouse bone marrow cells by decreasing micronucleus formation. Cct fruits extract against cyclophosphamide cpinduced dna damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Premature ovarian failure and infertility are adverse effects of cancer therapies. Simultaneous treatment with these plants significantly reduced the genotoxicity induced by lead administration and the powerful protection was observed with 5% powdered turmeric. Unlike anthracyclines, cyclophosphamideinduced cardiotoxicity does not appear to be cumulative.
In addition, when given in high doses as a part of a myeloablative. Caution should be exercised when handling and preparing cyclophosphamide for injection, usp lyophilized powder, or bottles containing cyclophosphamide tablets. Cardiotoxic side effect of cyclophosphamide is a major challenge. The mechanism may involve direct injury to the endothelium by phosphoramide mustard, an active metabolite of cyclophosphamide. Protective effects of essential oils as natural antioxidants. The mechanism underlying chemotherapymediated depletion. The present study was undertaken to evaluate the natural protective efficacy of methanolic grape seed extract gse against cpinduced genotoxicity and histopathologically changes of liver and colon cancer cells in mice. Prevention of cyclophosphamideinduced micronucleus formation in mouse bone marrow by solanum lycopersicum extract. Clinical application of cyclophosphamide cp as an anticancer drug is often limited due to its toxicity.
Protective action against chemicalinduced brazilian journal. Cp is metabolized mainly in the liver by cytochrome p450 system into acrolein which is the proximate toxic metabolite. Both forms of cyp induced an increase in chromosomal aberrations and sces at the different sampling time. Pathogens free fulltext protective effects of evening. Pdf coffee mitigates cyclophosphamideinduced genotoxic. Invitro evidence for cyclophosphamide induced cardiotoxicity. Molecular mechanism involved in cyclophosphamideinduced. Cyclophosphamide cp is a wellknown antineoplastic agent. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases. The objective of the study is to evaluate the protective role of nanose against cp induced hepatotoxicity and genotoxicity in swiss albino mice. Cyc is widely used at high dose for chemotherapy of various forms of cancer bronchial, breast and ovarian cancer, lymphomas. It is one of the most potent immunosuppressive drugs available. Pol j antioxidant enzymes, lipid peroxidation rate and lipid pharmacol, 56.
Therapeutic use of cyclophosphamide and its cytotoxic action. Another metabolite chloroacetaldehyde caa associated with nephrotoxicity, has not been investigated for toxicity in the bladder and this study investigates the effects of acrolein and caa on human urothelial. We previously reported thathesperidin,acitrusbio avonoid,mayhaveantioxidative activity and can reduce the genotoxicity induced by cp in mouse bone marrow cells by decreasing micronucleus formation. This experimental study was performed to investigate the chemoprotective effects of epo in the liver and. Protective eff ects of salvia offi cinalis extract against. Protective eff ects of salvia offi cinalis extract against cyclophosphamideinduced genotoxicity and oxidative stress in rats 648 extract was transferred to centrifuge tubes, centrifuged for 10 min 5000 rpm, and subsequently fi ltered through a fi lter paper into a 100ml fl ask. In this study, ellagic acid ea, a naturally occurring plant polyphenol, was evaluated for its antigenotoxicity and antioxidant efficacy against the cpminduced renal oxidative stress and genotoxicity in swiss albino mice. Protective effect of liposomal formulation of tuftsin a naturally occurring tetrapeptide against cyclophosphamideinduced genotoxicity and oxidative stress in mice. Follow the directions on your prescription label carefully, and ask your. Cyclophosphamide induced cystitis and bladder cancer in patients with wegener granulomatosis. Arif k, ejaj a, maroof a, azmat ak, arun c, fatima n, et al. Water intoxication induced by lowdose cyclophosphamide in two patients with systemic lupus erythematosus. The protective effect of ellagic acid january 2012 molecular and cellular biochemistry. Cyclophosphamideinduced nephrotoxicity, genotoxicity, and.
Protective action against chemicalinduced brazilian journal of pharmacognosy genotoxicity and free radical scavenging activities of stryphnodendron adstringens barbatimao leaf extracts plinio r. Giesy,4,5,6 zhiming kong,1 yibin cui1 1state key laboratory of pollution control and resource reuse, school of the environment, nanjing university, nanjing 210093, peoples republic of china. Preclinical perspective of cyclophosphamide induced cardiotoxicity 4. Cytoxan cyclophosphamide for injection, usp cytoxan. Aegle marmelos, plant known for its medicinal importance since ancient times and every part of the plant has been used for curing different diseases. Citrus extract at a dose of 400 mg kg1 reduced mnpces 2. Cyclophosphamide induced lipid peroxidation and changes. Protective eff ects of salvia offi cinalis extract against cyclophosphamide induced genotoxicity and oxidative stress in rats 648 extract was transferred to centrifuge tubes, centrifuged for 10 min 5000 rpm, and subsequently fi ltered through a fi lter paper into a 100ml fl ask. Cyclophosphamide n,nbis2chloroethyltetrahydro2h1,3,2oxazaphosphorin2amine 2oxide. Cyclophosphamide therapy is associated with minor transient serum enzyme elevations and has been linked to rare cases of acute liver injury. Possible genoprotective effect of citrullus colocynthis l. Due to its toxicity, it is replaced as soon as possible by less toxic drugs. Cct fruits extract against cyclophosphamide cp induced dna damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage.
Omega3 fatty acids modulate cyclophosphamide induced. The prevalence of micronuclei, the extent of lipid peroxidation, and the status of the antioxidant enzymes, superoxide dismutase sod, catalase cat, glutathione peroxidase gpx in both liver and serum of mice were used. We report a case of cyclophosphamideinduced cardiotoxicity in a patient with normal cardiac functions before chemotherapy. The objective of the study is to evaluate the protective role of nanose against cpinduced hepatotoxicity and genotoxicity in swiss albino mice. Although the precise mechanism of cpinduced testicular toxicity is still. Preclinical perspective of cyclophosphamideinduced cardiotoxicity 4. A 66yearold caucasian woman with a mediastinal mass diagnosed with burkitt. These genotoxic substance interact at a specific location or base sequence of the dna structure causing lesions, breakage, fusion, deletion, missegregation or non. Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs. Since there is no escaping of using such medications in spite of. Mechanism of genotoxicity the damage to the genetic material is caused by the interactions of the genotoxic substance with the dna structure and sequence. Jul 14, 2014 cardiac toxicity is one of the lifethreatening complications of cancer therapy.
Cyclophosphamide fda prescribing information, side effects. The clinical use of cyclophosphamide and ifosfamide is limited by a resultant bladder toxicity which has been attributed to the metabolite acrolein. Cyclophosphamide, a nitrogen mustard, is an alkylating agent from the oxazophosphorine group figure 1. Ginseng has often been clinically used with cp in china, but whether and how. Cytoxan tablets cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide. Amelioration of the cyclophosphamide induced genotoxic damage. Cyclophosphamide is a white crystalline powder with the molecular formula c 7 h 15 cl 2 n 2 o 2 p h 2. Dec 04, 2019 cyclophosphamide cp is a frequently used drug for its anticancer and immunosuppressive potential. Manual of vascular plants of northeastern united states and. As an immune suppressor it is used in nephrotic syndrome. Although not all of these side effects may occur, if they do occur they may need medical attention. With increased success rate of cancer treatment, due in part to the aggressive use of. Evaluation of cyclophosphamideinduced genotoxicity and cytotoxicity in cultured human l ymphocytes ravindra m samarth 1,2, t ooba khan 3, shweta srivas 4, pradyumna k mishra 2, rajnarayan r. Mice were preadministered with different doses of cct via intraperitoneal injection for 7 consecutive days followed by.
Zataria, avishan, chemoprotective, micronucleus, cyclophosphamide. Along with its needed effects, cyclophosphamide may cause some unwanted effects. The parent compound is inactive in vivo and in vitro and exerts its biological activities through metabolites, mainly phosphoramide mustard, by hepatic microsomal enzymes. Regular and frequent laboratory evaluations are required to monitor kidney function, avoid drug induced bladder complications and screen for bone marrow toxicity. The effect of boron b on cyclophosphamide cyc induced damage in liver 1, kidney 2, heart 3, brain 4 and lung 5 of rats. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. The cyclophosphamide cyp belongs to class of oxazaphosphorines and it is an alkylating agent extensively used as an anticancer chemotherapeutic agent for childhood and adult malignancies 2, 3 and other benign diseases. Cyclophosphamide cp, a chemotherapeutic agent, is restricted due to its side effects, especially hepatotoxicity. Side effects requiring immediate medical attention. Dads was gavaged to rats once daily for 3 days at 100 mgkgday.
The most deleterious affects of cyp free radicals in vivo were genotoxic. Take cyclophosphamide at around the same time every day. Cyclophosphamide cp is a frequently used drug for its anticancer and immunosuppressive potential. Till date, pathophysiology of cyclophosphamideinduced cardiotoxicity is not clearly understood. Cyclophosphamide is an alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mgkg cp. Pdf cyclophosphamideinduced nephrotoxicity, genotoxicity. In the genotoxicity evaluation, mice received the extract 500, 1,000, or 2,000 mgkg orally while negative and positive controls were treated with saline solution 0. Genoprotective and genotoxic effects of thymoquinone bioline. All of the available evidence indicates that cyclophosphamide exerts its carcinogenic activity via a genotoxic mechanism mccarroll et al.
Ameliorative effect of peach seed extract on cyclophosphamide. Protective effects of boron on cyclophosphamide induced. Genotoxic and histopathological aspects of treatment with. Amelioration of the cyclophosphamide induced genotoxic damage in mice. In this study, ellagic acid ea, a naturally occurring plant polyphenol, was evaluated for its antigenotoxicity and antioxidant efficacy against the cpm induced renal oxidative stress and genotoxicity in swiss albino mice. Prophylactic efficacy of melatonin on cyclophosphamide.
Cyclophosphamide is effective against a wide spectrum of malignancies, such as leukemia, lymphoma, breast, lung, prostate, and ovarian cancers. Chemoprotective effects of carnosine against genotoxicity. The prevalence of micronuclei, the extent of lipid peroxidation, and the status of the antioxidant enzymes, superoxide dismutase sod, catalase cat, glutathione peroxidase gpx in both liver and serum of mice were used as intermediate biomarkers. Pdf evaluation of cyclophosphamideinduced genotoxicity. Here, we applied the metabolic activation system to a ddr and. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer, small cell lung cancer, neuroblastoma, and sarcoma.
Prevention of cyclophosphamideinduced micronucleus. Pdf investigating the protective effect of nigella. Ginseng alleviates cyclophosphamideinduced hepatotoxicity. Cyclophosphamide cp, an oxazophosphorine derivative of the classical alkylating agent nitrogen mustard, is commonly used in cancer chemotherapy. Herbal medicines remain an important component of the health care system. Cyclophosphamide cp, also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic. Cyc, is a cytotoxic bifunctional alkylating agent, belongs to the class of nitrogen mustards dollery, 1999, tripathi and jena, 2008. Antioxidant activity is the proposed mechanism for the chemoprotective effects of these natural products 10, 11. Lipid peroxidation induced by cd is known to be due to the attack of free radicals on the fatty acid component. Because cp is a wellknown genotoxic agent that induces mn.
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