Effects of the induction of hepatic microsomal metabolism on the toxicity of cyclophosphamide

Gurtoo, Hira L.; Bansal, Surendra K.; Pavelic, Zlatko P.; Struck, Robert F.

doi:10.1038/bjc.1985.10

Cited by 8 publications

(2 citation statements)

References 13 publications

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“…Intervention of CP metabolism has, therefore, been attempted by some investigators to reduce its toxicity. 12,39 In this regard, glutathione and glutathione inducers have been found to be effective in reducing CP toxicity. A number of sulfur-containing compounds that are apparently glutathione inducers have shown protection against CP-induced bladder and kidney toxicity.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice

Haque¹,

Bin-Hafeez²,

Ahmad³

et al. 2001

Hum Exp Toxicol

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Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs in spite of its toxic side effects including immunotoxicity, hematotoxicity, mutagenicity and a host of others. The present study was undertaken to assess the protective effects of total aqueous extract of a medicinal plant, Indian gooseberry (Emblica officinalis Gaertn.) in mice treated with CP. These protective effects were studied on immunological parameters and kidney and liver antioxidants. Plant extract treatment at a dose of 100 mg/kg body weight per os (p.o.) for 10 days resulted in the modulation of these parameters in normal as well as CP (50 mg/kg)-treated animals. Plant extract in particular was very effective in reducing CP-induced suppression of humoral immunity. Plant extract treatment in normal animals modulated certain antioxidants of kidney and liver. In CP-exposed animals, plant pretreatment provided protection to antioxidants of kidney. Not only were the reduced glutathione levels significantly (p<0.001) increased but plant extract treatment resulted in restoration of antioxidant enzymes in CP-treated animals. It is suggested that E. officinalis or its medicinal preparations may prove to be useful as a component of combination therapy in cancer patients under CP treatment regimen. Human & Experimental Toxicology (2001) 20, 643–650.

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Section: Discussionmentioning

confidence: 99%

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice

Haque¹,

Bin-Hafeez²,

Ahmad³

et al. 2001

Hum Exp Toxicol

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show abstract

“…Cyclophosphamide is inactive per se and requires microsomal mixed function oxidase-mediated metabolism to activated metabolites capable of binding covalently to nucleic acids and proteins. The commonly accepted scheme of cyclophosphamide metabolism involves intermediate formation of 4-hydroxy-CP which undergoes ring-opening to form aldophosphamide, an isomer of 4-hydroxy-CP (Gurtoo et al, 1985). Aldophosphamide is metabolized to phosphoramide mustard and acrolein (Murgo & Weinberger, 1993).…”

Section: Introductionmentioning

confidence: 99%

Antioxidants in Cancer Treatment

Nepomuceno¹

2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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Current Cancer Treatment-Novel Beyond Conventional Approaches 624 concern that antioxidants might reduce oxidizing free radicals created by radiotherapy and some forms of chemotherapy, and thereby decrease the effectiveness of the therapy. The authors that support the idea that administration of oral antioxidants is contraindicated during cancer therapeutics, suggest that a drug's ability to destroy micrometastases may be impaired by the addition of antioxidants and, this may result in an improved short-term tolerance to treatment followed by an increased long-term chance for recurrence. On the other hand, there are several articles showing no evidence of significant decreases in the efficacy of chemotherapy with antioxidant supplementation and that supplementation of antioxidant vitamins during cancer treatment is effective, increasing quality and life expectancy. Considering that the use of antioxidants during treatment is a very contentious issue, the purpose of this chapter is to review studies in humans to evaluate the use of these antioxidants as a therapeutic intervention in cancer patients, and their interactions with radiation therapy and chemotherapy. 2. Classes of agents used in cancer treatment that produce a reactive oxygen compound or free radical The ultimate clinical effectiveness of any anti-cancer drug requires that it kill malignant tumor cells in vivo at doses that allow enough cells in the patient's critical tissues (e.g., bone marrow, gastrointestinal tract) to survive so that recovery can occur. This is difficult to accomplish because, in general, anticancer drugs are most useful against malignant tumor with a high proportion of dividing cells, and some normal tissues such as the bone marrow and G1 tract also have a high cell-proliferation rate. Anticancer drugs used by themselves are primarily effective against high-growth-fraction tumors such as the leukemias and lymphomas. The most common malignant tumors, however, are "solid" tumors, including those of the colon, rectum, lung and breast. These tumors usually have a low proportion of dividing cells and therefore are less susceptible to treatment by drugs alone (Pratt, 1994). There are some standard methods of cancer treaments: surgery, chemotherapy, radiation therapy, immunotherapy and biologic therapy. Undoubtedly, chemotherapy and radiotherapy are the treatments to fight cancer with more side effects. Chemotherapy agents can be divided into several categories: alkylating agents (e.g., cyclophosphamide, ifosfamide), antibiotics which affect nucleic acids (e.g., doxorubicin, bleomycin), platinum compounds (e.g., cisplatin), mitotic inhibitors (e.g., vincristine), antimetabolites (e.g., 5-fluorouracil), camptothecin derivatives (e.g., topotecan), biological response modifiers (e.g., interferon), and hormone therapies (e.g., tamoxifen). The agents most noted for creating cellular damage by initiating free radical oxidants are the alkylating agents, the tumor antibiotics, and the platinum compounds (Lamson & Brignall, 1999). 2.1 Alkylating ...

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Introduction of Cyclophosphamide

Saxena

Kumar

2020

Fish Analysis for Drug and Chemicals Mediated Cellular Toxicity

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Effects of the induction of hepatic microsomal metabolism on the toxicity of cyclophosphamide

Cited by 8 publications

References 13 publications

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice

Antioxidants in Cancer Treatment

Introduction of Cyclophosphamide

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