The Effect of a Single Dose of Cyclophosphamide on the Jejunum of Specified Pathogenfree and Germfree Rats

Ecknauer, R.; Löhrs, U.

doi:10.1159/000197940

Cited by 18 publications

(3 citation statements)

References 20 publications

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“…A more likely possibility may be that cyclophosphamide has a direct effect on the gut that brings about these changes. Although frank gut ileus has not been reported with cyclophosphamide, the drug is known to produce structural and functional changes in gut mucosal cells (3,6,10). Thus, it is conceivable that bacterial and candidal overgrowth may occur in a manner similar to that seen with blind loops or dysmotility syndromes (5,14).…”

Section: Discussionmentioning

confidence: 99%

Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice

Ekenna¹,

Sherertz²

1987

Infect Immun

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Male ICR Swiss mice (2 to 3 months old) were fed Candida albicans in their drinking water for 3 days, followed by no treatment, antibiotics in their drinking water (daily), or immunosuppressants given by intraperitoneal injection (two to three times weekly) over a 3to 4-week period. The organs of animals were processed to determine the numbers of C. albicans and total aerobic bacteria per g of tissue. Untreated animals had mean Candida counts during the 1-month period of 102.3 CFU/g of cecum. Animals in six of eight antibiotic-treated groups had mean cecal Candida coun)ts higher than those of control animals (P < 0.05), with clindamycin-gentamicin producing the highest counts (104* CFU/g). Cyclophosphamide produced counts (104-3 CFU/g) which were higher (P < 0.05) than those resulting from methotrexate (103-°CFU/g) or steroid (102.7 CFU/g) treatment. Cyclophosphamide-clindamycin-gentamicin treatment was associated with the highest (P < 0.05) levels of Candida colonization (1065 CFU/g). Mice receiving immunosuppressants plus clindamycingentamicin were more likely to disseminate C. albicans than were mice receiving antibiotics alone (P < 0.001). Our findings suggest that colonization of the guts of mice by C. albicans can be facilitated by manipulating the aerobic, anaerobic, or both types of gut flora. The combiped effect of immunosuppressants on both Candida gut colonization and dissemination appears multifactorial and deserves further investigation.

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Section: Discussionmentioning

confidence: 99%

Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice

Ekenna¹,

Sherertz²

1987

Infect Immun

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“…One possible explanation for their location would be that the intestinal epithelium is an important site on the migration pathways of young T cells, perhaps because of the large amounts of antigen which may be present in the intestinal lumen (Ferguson, 1977). Although data on antigen excess, either microbial or alimentary, are not available, it is known that germ-free animals deprived of microbial antigens have low IEL counts (Glaister, 1973;Ecknauer and Lohrs, 1976) and that removal of food antigen from healthy animals does not induce a decrease of IEL counts (Ferguson, 1976); on the other hand, it is suggested that the increase of IEL counts in coeliac disease must be due to antigen stimulation (Mavromichalis et al, 1976). It might be hypothesised, therefore, that an increase of intestinal IEL could be occurring in malnutrition, in which intestinal infection, bacterial overgrowth in the small bowel, or partial digestion of food protein antigens is likely to occur.…”

Section: Discussionmentioning

confidence: 99%

Intraepithelial lymphocytes in the jejunal mucosa of malnourished rats.

Maffei¹,

Rodrigues²,

Camargo³

et al. 1980

Gut

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“…Other studies have also found that the levels of Lactobacillus and Bifdobacterium were reduced, while Enterococcus and Escherichia coli were increased in the intestinal tract of mice treated with cyclophosphamide. Tis could be one of the reasons for the variations in the absorption of DMAG [39,40].…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Development and Validation of an UHPLC-MS/MS Method for Quantification of DMAG in Rat Plasma and Its Application in a Preliminary Pharmacokinetic Study in Thrombocytopenia Rats

Li,

Wang,

Zhao

et al. 2023

Journal of Chemistry

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A preliminary study has shown that 3, 8-Di-O-methylellagic acid 2-O-glucoside (DMAG), an ellagic tannin from Sanguisorba officinalis L., has the potential in relieving thrombocytopenia. However, there is a lack of information on the pharmacokinetics of DMAG in thrombocytopenia rats. Therefore, we aimed to establish a simple, rapid, and sensitive UHPLC-MS/MS method for quantifying DMAG and study its pharmacokinetic behavior in this study. DMAG and hispidulin (internal standard, IS) were separated on an Acquity Shim-pack GIST column using 0.1% formic acid in water and acetonitrile as the mobile phase with a total run time of 5 min and gradient elution at a flow rate of 0.3 mL/min. The recovery and matrix effects of DMAG were within 94.85%–100.40% and 94.55%–102.46%, respectively. The intraday RSD and interday RSD were between 3.31% and 13.19%, accuracy RE was ≤6.69%, and stability RSD changes were 3.38%–8.78%. As for intragastric administration, with shortened Tmax (3.00 vs. 2.16 h), Cmax (25.67 vs. 35.38 ng/mL) was added for a 2 mg/kg dose after the establishment of the thrombocytopenia rat model. Relative to normal rats treated with 4 mg/kg, in thrombocytopenia rats treated with the same dose, Cmax (49.13 vs. 67.78 ng/mL), AUC(0–t) (234.60 vs. 318.17 ng·h/mL), and AUC(0–∞) (322.74 vs. 498.57 ng h/mL) increased, MRT (18.15 vs. 26.32 h) prolonged, Tmax (3.00 vs. 2.33 h) shortened, and CL/F (12746.50 vs. 8093.50 mL/h/kg) reduced. As for intravenous administration, Cmax (1679.54 ng/mL), AUC(0–t) (589.02 g·h/mL), and AUC(0–∞) (605.58 g·h/mL) were significantly increased in thrombocytopenia rats than that in normal rats (743.76 ng/mL for Cmax, 242.46 g·h/mL for AUC(0–t), and 245.19 g·h/mL for AUC(0–∞)). Vz/F and CL/F were remarkably decreased from 343196.86 to 194659.43 mL/kg for Vz/F and 8236.18 to 3326.01 mL/h/kg for CL/F with the model establishment, respectively. Overall, we successfully developed a reliable UHPLC-MS/MS method for determining DMAG levels in rat plasma. The pharmacokinetic difference could be attributed to the pathological state of the thrombocytopenia rats, which may affect the absorption, distribution, metabolism, and excretion of DMAG. These findings lay the foundation for further evaluating the clinical efficiency and safety of DMAG in the treatment of thrombocytopenia.

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The Effect of a Single Dose of Cyclophosphamide on the Jejunum of Specified Pathogenfree and Germfree Rats

Cited by 18 publications

References 20 publications

Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice

Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice

Intraepithelial lymphocytes in the jejunal mucosa of malnourished rats.

Development and Validation of an UHPLC-MS/MS Method for Quantification of DMAG in Rat Plasma and Its Application in a Preliminary Pharmacokinetic Study in Thrombocytopenia Rats

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