Resistance to cyclophosphamide therapy continues to be a major reason for treatment failure. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer, small cell lung cancer, neuroblastoma, and sarcoma. Cisplatin caused a significant decrease in gentamicin clearance. A mechanism for 1,4benzoquinoneinduced genotoxicity. Foods can enhance, delay, or decrease drug absorption. Protective effect of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats article in chemosphere 108 february 2014 with 229 reads how we measure reads. Serum specific kidney function parameters urea, uric acid, total protein, creatinine, and histopathology of kidney tissue were evaluated to access gentamicin induced. This mechanism protects cells from the deleterious effects of endogenous dna damage induced by hydrolysis, reactive. Effects of cisplatininduced nephrotoxicity on gentamicin.
Recent reports point to the critical role of metabolism in determining cell sensitivity to doxorubicin, a conventional drug used. Pb pretreatment 1 mm increased the number of necrotic 2fold and apoptotic cells 4fold after ndea treatment 0. Cyclophosphamide cp, also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. Genotoxicity and mutagenicity of rosmarinus officinalis labiatae essential oil in mammalian cells in vivo e. The higher inhibition of oxidative stress in brain and serum enzymes and metabolites by the garcinia indica fruit extract could be attributed to its significantly higher p cyclophosphamide induced. They need to be activated in the liver prior to exerting their cytotoxic activity. The effects of cisplatin induced nephrotoxicity on the pharmacokinetics of a renally excreted antibiotic, gentamicin, were studied in f344 rats. As part of the search for the mechanism of hormoneinduced carcinogenesis, various types of dna damage have been detected which have been induced by oestrogens in cellfree systems, in cells in culture, or in vivo.
Dailymed cyclophosphamide injection, powder, for solution. Nsaid nonspecifically inhibit cyclooxygenase cox, an enzyme involved in renal prostaglandin synthesis, and this inhibition is believed to promote compensatory vasodilatory disequi. These tests should enable the identification of hazard with respect to dna damage and fixation 8. A switching mechanism in doxorubicin bioactivation can be. Genotoxicity of the steroidal oestrogens oestrone and.
Cyclophosphamide induced sterility may be irreversible in some patients. This chapter covers some of the mechanisms implicated in resistance to the toxic and mutagenic effects of cyclophosphamide therapy in the laboratory and clinic. Although not fda approved, other kidney diseases caused by a disrupted immune system have been treated continued. Therefore, it is of great significance to establish relative defining guidance for safe assessment of botanicals. The present investigation was designed to investigate the protective effect of beta vulgaris l. Lowdose cyclophosphamideinduced acute hepatotoxicity. Mar 15, 2017 cyclophosphamide interferes with oogenesis and spermatogenesis.
Phenacetininduced mutations mainly consisted of point mutations rather than. In contrast, nongenotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects. Cyclophosphamide induced sister chromatid exchange in mouse primary bonemarrow and spleen cells solerniedziela et al. Selfdefense mechanisms against genotoxic chemicals. Genotoxicity is a concern associated with the use of mnps because it plays a major role in the initiation and progression of abnormalities. Oxidative stress is considered to be the key indirect mechanism of nminduced genotoxicity. Nevertheless, oestrogens have been postulated to act only as promoters of mammary carcinogenesis by receptormediated growth stimulation without consideration of their genotoxicity because these hormones failed to induce mutations in commonly used assays.
It is well tolerated and has potentially beneficial actions in reducing serum cholesterol 2 and the incidence of fatal heart attacks 3. Direct damage to dna is generally accepted as the main initiator of mutation and cancer induced by environmental carcinogens. Importance of genotoxicity studies genotoxicity studies can be defined as various invitro and invivo tests designed to identify any substance or compounds which may induce damage to genetic material either directly or indirectly by various mechanisms. Tremendous attentions have been attracted to the foods labeled with natural, green, organic, and nuisanceless conception of healthy diet. Diseases treated with this medication this medication is primarily used to treat cancers and nephrotic syndrome. A mechanism for 1,4benzoquinoneinduced genotoxicity ncbi. Cyclophosphamide cp, a chemotherapeutic agent, is restricted due to its side effects, especially hepatotoxicity. Immunomodulatory activity of methanolic extracts of ficus. The significant inmmunostimulant effect of the methanolic extracts of ficus glomerata roxb. The positive controls see table 2 produced the expected.
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. Genoprotective and genotoxic effects of thymoquinone bioline. Nnitrosodiethylamine ndeainduced genotoxicity and cytotoxicity was used in primary cultures of female rat hepatocytes in the presence of phenobarbital pb. Lcarnitine protect against cyclophosphamide induced skeletal and neural tube malformations in rat fetuses mahmood khaksary mahabady department of anatomy and embryology, school of veterinary medicine, shahid chamran university, ahvaz, iran. Drug induced dna damage and tumor chemosensitivity.
Genotoxicity is the mechanism by which cell injury is induced and cause direct alterations and modifications of the genetic material and includes dna damage, gene mutation, chromosomal effects and aberrations of genetic content. Mutagenic chemicals cause predominantly gene mutations, which are generally not lethal but can form a major threat to the integrity of chromosomes and viability of cells. Therapeutic use of cyclophosphamide and its cytotoxic. Hepatotoxicity may occur even after lowdose intravenous cyclophosphamide treatment. The in vitro micronucleus mnvit assay is a genotoxicity test for the detection of micronuclei mn in the cytoplasm of interphase cells. Mechanism of genotoxicity induced by targeted cytoplasmic irradiation. Therapeutic use of cyclophosphamide and its cytotoxic action. Although the survival rate of childhood leukemia is relatively high, those who do not respond to chemotherapy have very low prognostic outcome. Cyclophosphamide definition is an immunosuppressive and antineoplastic agent c7h15cl2n2o2p used especially in the treatment of lymphomas and some leukemias. Cyclophosphamide definition of cyclophosphamide by merriam. Immunotoxicity, genotoxicity and epigenetic toxicity of.
Nutrientdrug interactions nutritional disorders msd. Acute pneumocyte injury, polyadpribose polymerase activity, and pyridine nucleotide levels after in vitro exposure of murine lung slices to cyclophosphamide. Specific aspects of regulatory genotoxicity tests for pharmaceuticals ich s2a, april 1996. Purpose of genotoxicity assays assays even though inexpensive, have high statistical power and can be reproduced and have the ability to detect a wide variety of genotoxic endpoints. Thresholds of genotoxic and nongenotoxic carcinogens. 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. Base excision repair ber base excision repair ber is a cellular mechanism that repairs damaged dna throughout the cell cycle.
Review on genotoxicity, its molecular mechanisms and. Tamoxifen is an antiestrogen widely used with proven efficacy in the treatment of breast cancer in women 1. 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. It also allows the detection of a drugs potential to cause genotoxicity even in the early stage of drug. However, the most likely mechanism of nminduced genotoxicity is indirect, via intermediate biomolecules that either are involved in normal genome function or cell division, or attack dna, causing dna injury or chromosomal malformations. Mechanism of apoptosis induced by doxorubicin through the. Drug class cytotoxicimmunosuppressive mechanism of action drugs of this class suppress the natural immune system including b and t lymphocyte activity and function. To the best of our knowledge, this is the first report of severe, nonviral, liver inflammation developing within 24 hours of administration of lowdose intravenous cyclophosphamide 200 mg.
Insert iv into dominant arm, or if arteriovenous fistula or graft present, then opposite arm vital signs x 1, then prn. Genotoxicity and mutagenicity of rosmarinus officinalis. Clinical pharmacology of ifosfamide and metabolites. Ginseng alleviates cyclophosphamideinduced hepatotoxicity. It is one of the most potent immunosuppressive drugs available. Significance of chemical induced mutation for human health.
I j pharmacy life sciences cyclophosphamideinduced oxidative. Mechanisms of resistance to the toxicity of cyclophosphamide. Iljinsk family cyclocaryaceae, called sweet tea tree, is a wellknown edible and medicinal plant, which. A single dose of gentamicin 30 mgkg, iv was given to different groups of rats alone, at the same time as, or on day 4, 7, 15, or 29 following cisplatin administration 6 mgkg, iv. Thresholds of genotoxic and nongenotoxic carcinogens ncbi. Voorma, ingevolge het besluit van het college voor promoties. These tests enable hazard identification with respect to damage to dna and its fixation. Phenacetin acts as a weak genotoxic compound preferentially in the. Genotoxins are agents that can damage the dna sequence and chromosomal.
Citrus extract modulates genotoxicity induced by cyclophosphamide in mice bone marrow cells article pdf available in journal of pharmacy and pharmacology 574. Cyclophosphamide fda prescribing information, side effects. Pdf citrus extract modulates genotoxicity induced by. The main anticancer action of doxorubicin dox is believed to be due to topoisomerase ii inhibition and free radical generation. Molecular mechanisms involved in production of chromosomal aberrations one of the endpoints of genotoxicity is gene mutations. Effects of curcumin in combination with cyclophosphamide on. In vitro mammalian cell micronucleus test mnvit introduction 1. Ginseng has often been clinically used with cp in china, but whether and how. Our previous study has demonstrated that tas103, a topoisomerase inhibitor, induces apoptosis through dna cleavage and subsequent h 2 o 2 generation mediated by nadph oxidase activation h. Mechanisms of tamoxifeninduced genotoxicity and carcinogenicity. Not all patients with deterioration in pulmonary function tests have a progressive disease. Protective effect of boron on cyclophosphamide induced lipid.
Dose selection for the plate incorporation method was adequate based on the use of. Cyclophosphamide, a nitrogen mustard, is an alkylating agent from the oxazophosphorine group figure 1. Mechanism of action both drugs belong to the class of antineoplastics known as the alkylating agents. Evaluation on genotoxicity and teratogenicity of aqueous. Cisplatin and cyclophosphamide induced primordial follicle depletion is caused by direct damage to oocytes. Assessing the genotoxicity of two commonly occurring byproducts of.
Review on genotoxicity, its molecular mechanisms and prevention. Development of sterility appears to depend on the dose of cyclophosphamide, duration of therapy, and the state of gonadal function at the time of treatment. Jun 21, 2019 cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. Author summary in the united states, acute lymphoblastic leukemia all is the most common form of cancer among children. Cyclophosphamideinduced nephrotoxicity, genotoxicity, and. The study demonstrated that azoospermia developed approximately two to three months after the start of therapy, and was. Effect of cyclooxygenase inhibitors on gentamicininduced. S2 r1 step 5 genotoxicity testing and data interpretation for. Nnitrosodiethylamine genotoxicity in primary rat hepatocytes. Lcarnitine protect against cyclophosphamide induced skeletal.
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