Antioxidants cyclophosphamide

In vivo experimental evidences support the in vitro antioxidant effect of squalene. Senthilkumar et al. (2006) suggested that dietary-supplied squalene to experimental rats normalized the enzymic and nonenzymic antioxidants after cyclophosphamide-induced toxicity. The rats were induced to have normal cell toxicity in their heart by being fed by 150 mg cyclo-phosphamide/kg of rat. In experimental design, squalene treatment at... 

In animal studies, NAC has been shown to prevent hemorrhagic cystitis that results from administration of cyclophosphamide or its position isomer ifosfamide. Hemorrhagic cystitis results from the toxic effect of acrolein, a metabolic product of cyclophosphamide or its position isomer ifosfamide. The mechanism whereby NAC prevents this toxicity may be prevention of the intracellular depletion of antioxidants, such as GSH, by acrolein. Concomitant administration of NAC with cyclophosphamide or ifosfamide does not impair antineoplastic activity, because both anticancer drugs are inactive until they are metabolized by the liver to their phosphoramide mustard metabolites. 

Fat-soluble vitamins, in addition to their antioxidative effects on lipids, appear to exert a general protective effect in animals. Vitamin A and beta-carotenes protect lab animals from toxicity of citral, cyclophosphamide and some hydrocarbons (Seifter et al, (A2.) In related but independent studies, it was observed that high levels of vitamin A inhibit tumorogenesis and that low levels of vitamin A appear to enhance tumorogenesis (Baird, (1 ). vitamin E inhibited chemically-induced carcinogenesis in test systems (Shamberger, ) and also reduced the susceptibility of rats to cigarette smoke (Chow,... 

Patel JM, Block ER. 1985. Cyclophosphamide-induced depression of the antioxidant defense mechanisms of the lung. Exp Lung Res 8 153-165. 

The oxidants are products of normal cellular respiration that are normally counterbalanced by an antioxidant defense system that prevents tissue destruction. The antioxidants include superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, and a-tocopherol (vitamin E). Antioxidants are ubiquitous in the body. Hy-peroxia produces toxicity by overwhelming the antioxidant system. There is experimental evidence that a number of drugs and chemicals produce lung toxicity through increasing production of oxidants (e.g., bleomycin, cyclophosphamide, nitrofurantoin, and paraquat) and/or by inhibiting the antioxidant system (e.g., carmustine, cyclophosphamide, and nitrofurantoin). ... 

There is no known antidote to paraquat or diquat poisoning. Some clinicians have used antioxidants such as vitamins C or E, N-acetyl cysteine, nitric oxide donors, and a combination of cyclophosphamide and corticosteroids to prevent inflammation and pulmonary fibrosis in severe cases. However, the effectiveness of these treatments appears to be marginal. If the chemical has been ingested, the main treatment is to prevent further absorption from the gastrointestinal tract. This is accomplished by the standard methods gastric lavage with safine solution to wash the substance from the stomach or ingestion of activated charcoal or Fuller s earth to act as absorbents. Since one of the effects of both paraquat and... 

Examples of activated double bond electrophiles include a, 3-unsaturated carbonyl compounds, quinones, quinoneimines, quinonemethides and diiminoquinones as shown in Fig. 10.32B. These electrophilic intermediates are highly polarized and can react with nucleophiles in a 1,4-Michael-type addition at the more electrophilic or 3-oarbon of the activated double bond intermediate to the addition product (Fig. 10.32A). Specific examples of activated double bond electrophiles that have been proposed for the anticancer drug leflunamide, the food antioxidant butylated hydroxytoluene, acetaminophen, the antiandrogen flutamide, the anticonvulsant felbamate and the cytotoxic cyclophosphamide as shown in Fig. 10.32C. The bioinaotivation pathways for these electrophilic intermediate can involve either direct addition, with or without transferases, depending upon the degree of polarization and reactivity of the electrophilic intermediate (hard vs soft electrophiles). 

Venkatesan, N. and Chandrakasan, G., Modulation of cyclophosphamide-induced early Irmg injury by curcumin, an anti-inflammatory antioxidant. Mol Cell Biochem., 142 (1), 79-87, 1995. 

Mathew S, Kuttan G (1996) Antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity. Amala Research Bulletin 16 113-121... 

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