Prevention by Chitosan of Myelotoxicity, Gastrointestinal Toxicity and Immunocompetent Organic Toxicity Induced by 5‐Fluorouracil without Loss of Antitumor Activity in Mice

Kimura, Yoshiyuki; Okuda, Hiromichi

doi:10.1111/j.1349-7006.1999.tb00813.x

Cited by 44 publications

(31 citation statements)

References 35 publications

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“…Biliary excretion of CPT-11 as its inactive glucuronide, and the reversal of this glucuronidation by enzymes produced by the intestinal flora, means that h-glucuronidase activity is influential in the development of CPT-11 toxicity. Although it is an emerging nutritional concept to treat certain types of refractory diarrhea using prebiotics (44,45), and this would also seem relevant in methotrexate and 5-fluoruracil chemotherapy (15,35), our results suggested that caution may need to be exercised when employing prebiotic treatment in conjunction with CPT-11. Prebiotic oligosaccharides doubled h-glucuronidase activity in cecal contents, which would be expected to increase the formation of SN38, the toxic metabolite of CPT-11, and thus, to aggravate rather than ameliorate intestinal injury.…”

Section: Discussionmentioning

confidence: 89%

“…Feeding oligofructose and/or inulin reduced genetically or chemically induced colitis in animal models (24,25), as well as in some emerging studies in human inflammatory bowel disease (43). There are only a few reports on the effects of dietary fibers on chemotherapy-induced intestinal toxicity, specifically with methotrexate and 5-fluoruracil (14,15). The case of CPT-11 is unique.…”

Section: Discussionmentioning

confidence: 99%

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Nutritional Modulation of Antitumor Efficacy and Diarrhea Toxicity Related to Irinotecan Chemotherapy in Rats Bearing the Ward Colon Tumor

Xue¹,

Sawyer²,

Field

et al. 2007

Clinical Cancer Research

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Purpose: To evaluate and compare the influence of dietary elements on cancer progression, chemotherapy efficacy, and toxicity, particularly severe, late-onset diarrhea related to irinotecan (CPT-11) treatment. Experimental Design: We used laboratory rats fed a standardized basal diet,Ward colon tumor, and CPT-11therapy for the study of CPT-11^induced diarrhea. Dietary interventions were selected from nutrients already established to modify other forms of colitis and which have been hypothesized to mitigate chemotherapy-induced gastrointestinal injury (glutamine, n-3 fatty acids, prebiotic oligosaccharides). Animals adapted to test diets were treated with CPT-11at the maximum tolerated dose (125 mg/kg Â 3 days) and diarrhea was followed continuously for 1week.Results: The inclusion of n-3 fatty acids in the diet (5%, w/w of total fat) suppressed tumor growth and enhanced CPT-11's efficacy; this treatment did not affect the incidence or severity of diarrhea. By contrast, oral glutamine bolus (0.75 g/kg) administered prior to each CPT-11 treatment reduced the incidence of severe diarrhea (34.1 F 4.7% versus 53.8 F 4.2%, P < 0.005) and decreased the area under the curve of diarrhea score (16.5 F 1.0 versus 18.8 F 0.5, P < 0.05).Identical results were obtained with i.v. bolus glutamine administration. Glutamine treatment did not alter CPT-11's antitumor efficacy. The addition of prebiotic oligosaccharides to the diet (8%, w/w of diet) did not mitigate the severity of diarrhea, and it raised the activity of h-glucuronidase in cecal contents, a key bacterial enzyme mediating CPT-11^related intestinal toxicity. Conclusion: Our experiments suggest that glutamine and n-3 fatty acids might be potentially useful adjuncts to CPT-11treatment.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Nutritional Modulation of Antitumor Efficacy and Diarrhea Toxicity Related to Irinotecan Chemotherapy in Rats Bearing the Ward Colon Tumor

Xue¹,

Sawyer²,

Field

et al. 2007

Clinical Cancer Research

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“…In a mouse sarcoma model, dietary fiber chitosan delayed onset of 5-fluorouracil (5-FU)-induced diarrhea and selectively inhibited 5-FU uptake into the small intestine without affecting 5-FU incorporation into the tumor [66]. In a rat model, while L. plantarum 299v did not prevent diarrhea or reduce bacterial translocation, it did reduce 5-FU-related anorexia, weight loss and intestinal load of facultative anaerobes [67].…”

Section: Adjuvant Treatment-related Toxicitymentioning

confidence: 99%

Probiotics, Prebiotics, Synbiotics: Is There Enough Evidence to Support Their Use in Colorectal Cancer Surgery?

Peitsidou

Karantanos²,

Theodoropoulos³

2012

Dig Surg

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Background/Aims: Pro-/pre-/synbiotics supplementation seems to provide beneficial effects in various aspects of abdominal pathology. Skepticism exists with respect to their effects on colorectal cancer (CRC) patients. This review presents the potential clinical applications of pro-/pre-/synbiotics in CRC surgery. Methods: A literature search of electronic databases was conducted and all studies published on ‘probiotics’, ‘prebiotics’ and ‘synbiotics’ were collected. Among them, the ones referring to CRC and which had any clinical relevance offering information on perioperative parameters were used. Results: Incorporation of pre-/pro-/synbiotic formulations in the preoperative mechanical bowel preparation cannot be supported by the current evidence. Limited clinical studies may be promising in supporting their potentially protective role against postoperative infectious complications. Encouraging are the results on their protective role against adjuvant (chemo)radiation-induced diarrhea. Such supplementation may also hold promise to improve postcolectomy gastrointestinal related quality of life. Conclusions: Despite the positive results and plethora of agents, bacterial combinations and concentrations, the inconsistency in administration, the inhomogeneity of comparison groups and lack of stringent clinical endpoints remain obstacles in the effort to establish a definitive clinical strategy at this time. Further work is warranted to gain a keen understanding of their clinical value in CRC patients.

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“…c) Antitumour activity: Recently conducted research on antitumour effect of chitosan showed that the low-molecular-weight watersoluble chitosans and oligochitosans might be useful in preventing tumor growth, partly through enhancing cytotoxic activity against tumors as an immunomodulator 87 .…”

Section: Biological Applicationsmentioning

confidence: 99%

Untitled

2013

IJPSR

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Chitosan is a natural polysaccharide which is widely exploited for its various applications. It has received much attention as a functional biopolymer especially in pharmaceutics and medicine because of its better biodegradability, biocompatibility, versatility and availability. The unique biological applications of chitosan are attributed to these specific properties. The chemical and biological modification of chitosan is mainly done to increase its solubility in aqueous solutions and absorbability in the in vivo system. A variety of chemical modifications are employed to modify this carbohydrate polymer. The modifications of chitosan are influenced by several factors such as molecular weight of chitosan, viscosity, reaction conditions etc. The selective biological applications include antimicrobial, hypocholesterolemic, antitumor, anti-inflammatory, antioxidant, angiotensin-I-converting enzyme (ACE) inhibition, excluding toxins from the intestines, reducing heavy-metal poisoning in humans, mucoadhesive haemostatic, analgesic, radio-protective properties, preventing tooth decay and tooth diseases and immunity enhancing activities. It is also widely useful in biomedical industries and food industries. The present paper reviews the current trend of investigation on various useful modifications on chitosan and their applications in various fields. INTRODUCTION:Natural polysaccharides are being utilized more and more in the markets for the reason that they show biodegradability, biocompatibility, versatility, and are found plentiful in nature. The diversity of natural polysaccharides provides the chemist with a broad spectrum of raw materials that can be used in many biological applications.

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Prevention by Chitosan of Myelotoxicity, Gastrointestinal Toxicity and Immunocompetent Organic Toxicity Induced by 5‐Fluorouracil without Loss of Antitumor Activity in Mice

Cited by 44 publications

References 35 publications

Nutritional Modulation of Antitumor Efficacy and Diarrhea Toxicity Related to Irinotecan Chemotherapy in Rats Bearing the Ward Colon Tumor

Nutritional Modulation of Antitumor Efficacy and Diarrhea Toxicity Related to Irinotecan Chemotherapy in Rats Bearing the Ward Colon Tumor

Probiotics, Prebiotics, Synbiotics: Is There Enough Evidence to Support Their Use in Colorectal Cancer Surgery?

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