Cyclophosphamide induced genotoxicity mechanism pdf free

Chemoprotective effects of zataria multiflora against genotoxicity. Along with its needed effects, cyclophosphamide may cause some unwanted effects. Protective effects of boron on cyclophosphamide induced. Data of 1018 patients 725 women293 men treated with cyc were evaluated in this retrospective study. Pdf investigating the protective effect of nigella. Ameliorative effect of peach seed extract on cyclophosphamide. Pdf coffee mitigates cyclophosphamideinduced genotoxic. Preclinical perspective of cyclophosphamide induced cardiotoxicity 4. Protective effect of liposomal formulation of tuftsin a naturally occurring tetrapeptide against cyclophosphamideinduced genotoxicity and oxidative stress in mice. Cyclophosphamide cp, also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. Original contribution modulatory effects of total extract of. As an immune suppressor it is used in nephrotic syndrome.

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. It produces highly active carbonium ion, which reacts with the extremely electronrich centers of nucleic acids and proteins. Cyclophosphamide cp is an alkylating agent widely used in cancer chemotherapy. Pdf protective effect of extracts of teucrium polium and. 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. Cyclophosphamide is effective against a wide spectrum of malignancies, such as leukemia, lymphoma, breast, lung, prostate, and ovarian cancers.

Cardiac toxicity is one of the lifethreatening complications of cancer therapy. All of the available evidence indicates that cyclophosphamide exerts its carcinogenic activity via a genotoxic mechanism mccarroll et al. 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. Genotoxicity assessment of saline extract from pilosocereus. The effect of boron b on cyclophosphamide cyc induced damage in liver 1, kidney 2, heart 3, brain 4 and lung 5 of rats. The most deleterious affects of cyp free radicals in vivo were genotoxic. Jun 01, 2011 the aim of this article is to elucidate the mechanism by which eicosapentaenoic acid epa acts against cyclophosphamide cp. Although not all of these side effects may occur, if they do occur they may need medical attention. Prevention of cyclophosphamideinduced micronucleus formation in mouse bone marrow by solanum lycopersicum extract. Cytoxan tablets cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide anhydrous. The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide cp in mice. 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 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. 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. 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. Cytoxan cyclophosphamide for injection, usp cytoxan tablets. 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. Systemic anticancer treatments may exert their own toxic effects or can aggravate adverse effects of other drugs. Administration of cyclophosphamide depleted the gsh level in liver.

Molecular mechanism involved in cyclophosphamideinduced. 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. Evening primrose oil epo contains several phytoconstituents with potent antioxidant and antiinflammatory activities. The mechanism underlying chemotherapymediated depletion. Cyclophosphamideinduced nephrotoxicity, genotoxicity, and damage in kidney genomic dna of swiss albino mice. Cyclophosphamide fda prescribing information, side effects.

Simultaneous treatment with these plants significantly reduced the genotoxicity induced by lead administration and the powerful protection was observed with 5% powdered turmeric. Genoprotective and genotoxic effects of thymoquinone bioline. 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 effect of selenium nanoparticle against. Protective effects of boron on cyclophosphamide induced lipid. Zataria, avishan, chemoprotective, micronucleus, cyclophosphamide. Cyclophosphamide cp is commonly used chemotherapeutic and immunosuppressive agent for the treatment of a wide range of neoplastic as well as some utoimmune diseases. Mice were preadministered with different doses of cct via intraperitoneal injection for 7 consecutive days followed by. 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. Cyc, is a cytotoxic bifunctional alkylating agent, belongs to the class of nitrogen mustards dollery, 1999, tripathi and jena, 2008. Dec 04, 2019 cyclophosphamide cp is a frequently used drug for its anticancer and immunosuppressive potential.

Arif k, ejaj a, maroof a, azmat ak, arun c, fatima n, et al. Cyclophosphamide cpm, an alkylating agent is used as an immunosuppressant in rheumatoid arthritis and in the treatment of several cancers as well. In addition, when given in high doses as a part of a myeloablative. Avocado fruit persea americana mill exhibits chemoprotective potentiality against cyclophosphamide induced genotoxicity in human lymphocyte culture. Possible genoprotective effect of citrullus colocynthis l. Cadmiuminduced genotoxicity, cytotoxicity and lipid peroxidation in allium sativum and. It may be concluded that turmeric and myrrh are useful herbal remedies, especially for controlling oxidative damages and genotoxicity induced by lead acetate intoxication.

Cyc is widely used at high dose for chemotherapy of various forms of cancer bronchial, breast and ovarian cancer, lymphomas. Protective effects of eicosapentaenoic acid on genotoxicity. To assess bladder toxicity of cyclophosphamide cyc and uroprotective effect of mesna in rheumatic diseases. 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. Cadmiuminduced genotoxicity, cytotoxicity and lipid. Omega3 fatty acids modulate cyclophosphamide induced. Clinical application of cyclophosphamide cp as an anticancer drug is often limited due to its toxicity.

Cyclophosphamide comes as a tablet to take by mouth once a day. 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. The parent compound is inactive in vivo and in vitro and exerts its biological activities through metabolites, mainly phosphoramide mustard, by hepatic microsomal enzymes. Cyclophosphamide cp, an oxazophosphorine derivative of the classical alkylating agent nitrogen mustard, is commonly used in cancer chemotherapy. Protective effects of eicosapentaenoic acid on genotoxicity and oxidative stress of cyclophosphamide in mice mei li,1 qin zhu,2 changwei hu,3 john p. Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic.

Cytoxan cyclophosphamide for injection, usp cytoxan. Cyclophosphamide cp, a chemotherapeutic agent, is restricted due to its side effects, especially hepatotoxicity. Cyclophosphamide, a nitrogen mustard, is an alkylating agent from the oxazophosphorine group figure 1. Take cyclophosphamide at around the same time every day. Ginseng alleviates cyclophosphamideinduced hepatotoxicity. This experimental study was performed to investigate the chemoprotective effects of epo in the liver and. Protection by turmeric and myrrh against liver oxidative.

Pathogens free fulltext protective effects of evening. Protective action against chemicalinduced brazilian. 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. Both forms of cyp induced an increase in chromosomal aberrations and sces at the different sampling time. Due to its toxicity, it is replaced as soon as possible by less toxic drugs. Prevention of cyclophosphamideinduced micronucleus. The clinical use of cyclophosphamide and ifosfamide is limited by a resultant bladder toxicity which has been attributed to the metabolite acrolein. Antioxidant activity is the proposed mechanism for the chemoprotective effects of these natural products 10, 11. Till date, pathophysiology of cyclophosphamide induced cardiotoxicity is not clearly understood. In the present set of investigation, antimutagenic effect of aegle marmelos bark amb extract. Lipid peroxidation induced by cd is known to be due to the attack of free radicals on the fatty acid component of membrane lipids. 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.

Protective effect of diallyl disulfide on cyclophosphamide. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer, small cell lung cancer, neuroblastoma, and sarcoma. Incidence of cyclophosphamideinduced urotoxicity and. Research article the mitigating effect of citrullus. Cyclophosphamide is a white crystalline powder with the molecular formula c 7 h 15 cl 2 n 2 o 2 p h 2. Amelioration of the cyclophosphamide induced genotoxic. The objective of the study is to evaluate the protective role of nanose against cp induced hepatotoxicity and genotoxicity in swiss albino mice. Cardiotoxic side effect of cyclophosphamide is a major challenge. 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. Pdf evaluation of cyclophosphamideinduced genotoxicity and. Pdf cyclophosphamide is one of the chemotherapeutics for cancer, which is used to treat several types of cancer, however this drug has severe side.

Genoprotective effects of origanum vulgare ethanolic extract against. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mgkg cp. Cyclophosphamide is an alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer. Amelioration of the cyclophosphamide induced genotoxic damage in mice. Genotoxic and histopathological aspects of treatment with. Invitro evidence for cyclophosphamideinduced cardiotoxicity. Hepatoprotective effects of zataria multiflora ethanolic. After the mice were sacrificed on day 30 liver and colons were removed, the. Cyclophosphamide cp is a wellknown antineoplastic agent. 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. Pdf cyclophosphamideinduced nephrotoxicity, genotoxicity.

Kinaseindependent inhibition of cyclophosphamideinduced. Citrus extract at a dose of 400 mg kg1 reduced mnpces 2. We report a case of cyclophosphamide induced cardiotoxicity in a patient with normal cardiac functions before chemotherapy. This experimental study was performed to investigate the chemoprotective effects of epo in the liver and pancreas of cpintoxicated mice. Because cp is a wellknown genotoxic agent that induces mn. Novel insights into the mechanism of cyclophosphamide. Dads was gavaged to rats once daily for 3 days at 100 mgkgday.

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. These genotoxic substance interact at a specific location or base sequence of the dna structure causing lesions, breakage, fusion, deletion, missegregation or non. Cyclophosphamide induced lipid peroxidation and changes. Cyclophosphamide induced cystitis and bladder cancer in patients with wegener granulomatosis. Cyclophosphamide cp is a frequently used drug for its anticancer and immunosuppressive potential. Water intoxication induced by lowdose cyclophosphamide in two patients with systemic lupus erythematosus. Ginseng has often been clinically used with cp in china, but whether and how. Cyclophosphamide therapy is associated with minor transient serum enzyme elevations and has been linked to rare cases of acute liver injury. Pdf evaluation of cyclophosphamideinduced genotoxicity. The protective effect of ellagic acid january 2012 molecular and cellular biochemistry. Unlike anthracyclines, cyclophosphamideinduced cardiotoxicity does not appear to be cumulative. 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. Chemoprotective effects of carnosine against genotoxicity. Lipid peroxidation induced by cd is known to be due to the attack of free radicals on the fatty acid component.

It is one of the most potent immunosuppressive drugs available. Amelioration of the cyclophosphamide induced genotoxic damage. Shortterm comparative study of the cyclophosphamide. Cyclophosphamide n,nbis2chloroethyltetrahydro2h1,3,2oxazaphosphorin2amine 2oxide.

A 66yearold caucasian woman with a mediastinal mass diagnosed with burkitt. Invitro evidence for cyclophosphamide induced cardiotoxicity. The aim of this article is to elucidate the mechanism by which eicosapentaenoic acid epa acts against cyclophosphamide cp. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases. 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.

The mechanism may involve direct injury to the endothelium by phosphoramide mustard, an active metabolite of cyclophosphamide. 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. Follow the directions on your prescription label carefully, and ask your. Cp is metabolized mainly in the liver by cytochrome p450 system into acrolein which is the proximate toxic metabolite.

Omega3 fatty acids modulate cyclophosphamide induced markers. Till date, pathophysiology of cyclophosphamideinduced cardiotoxicity is not clearly understood. Acute pneumocyte injury, polyadpribose polymerase activity, and pyridine nucleotide levels after in vitro exposure of murine lung slices to cyclophosphamide. 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. Caution should be exercised when handling and preparing cyclophosphamide for injection, usp lyophilized powder, or bottles containing cyclophosphamide tablets.

Therapeutic use of cyclophosphamide and its cytotoxic. Preclinical perspective of cyclophosphamideinduced cardiotoxicity 4. Therapeutic use of cyclophosphamide and its cytotoxic action. Incorporation of metabolic activation potentiates cyclophosphamide. These data support that enhanced lipid peroxidation in v. 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. Cyclophosphamide is used to treat cancers and autoimmune diseases. Since there is no escaping of using such medications in spite of. Regular and frequent laboratory evaluations are required to monitor kidney function, avoid drug induced bladder complications and screen for bone marrow toxicity.

Herbal medicines remain an important component of the health care system. With increased success rate of cancer treatment, due in part to the aggressive use of. Cytoxan tablets cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide. 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. Dads against cyclophosphamide cpinduced testicular toxicity in male rats. Here, we applied the metabolic activation system to a ddr and. Protective effects of essential oils as natural antioxidants. Manual of vascular plants of northeastern united states and. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Pol j antioxidant enzymes, lipid peroxidation rate and lipid pharmacol, 56.

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. Jul 14, 2014 cardiac toxicity is one of the lifethreatening complications of cancer therapy. Mechanism of genotoxicity the damage to the genetic material is caused by the interactions of the genotoxic substance with the dna structure and sequence. 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. Protective action against chemicalinduced brazilian journal. Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards.

Premature ovarian failure and infertility are adverse effects of cancer therapies. Protective eff ects of salvia offi cinalis extract against. The objective of the study is to evaluate the protective role of nanose against cpinduced hepatotoxicity and genotoxicity in swiss albino mice. Side effects requiring immediate medical attention. Handle and dispose of cyclophosphamide in a manner consistent with other cytotoxic drugs. Prophylactic efficacy of melatonin on cyclophosphamide.