The plasma of 5-Fluorouracil (5-FU) (100 mg/kg, i.v.) pharmacokinetics in rats treated with and without MMP-8 inhibitor then delivered to whole pelvic irradiation with 2 Gy.

<p>AUC: area under the plasma concentration <i>vs.</i> time curve; t_1/2: terminal elimination phase half-life; Cmax: maximum observed plasma concentration; MRT: mean residence time; CL: total plasma clearance; Vss: volume of distribution at steady state.</p><p>*The mean difference is significant at the 0.05 level in comparison to the whole pelvic irradiation with solvent and 5-FU group.</p

The area under the concentration vs. time curve (AUC) of 5-fluorouracil (5-FU) 100 mg/kg administered to rats in the control, 0.5-Gy and 2-Gy groups.

<p>The transverse axis illustrates time in minutes and the vertical axis represents the concentration of 5-FU. (A) Plasma. (B) Bile. Each group's data was collected from six rats.</p

Intracellular 5-fluorouracil (5-FU) levels for 50 µM 5-FU treated HepG2 (Human liver tumor-derived cells possessing biochemical profiles characteristic of normal hepatocytes) with or without 10 µg/mL recombinant MMP-8 by high performance liquid chromatography.

<p>Intracellular 5-fluorouracil (5-FU) levels for 50 µM 5-FU treated HepG2 (Human liver tumor-derived cells possessing biochemical profiles characteristic of normal hepatocytes) with or without 10 µg/mL recombinant MMP-8 by high performance liquid chromatography.</p

The cytokines respond to irradiation (RT) and 5-fluorouracil (5-FU) in plasma for control, RT 2 Gy alone, 5-FU alone, RT 0.5 Gy followed by 5-FU and RT 2 Gy followed by 5-FU groups.

<p>(A) The level of transforming growth factor beta 1 (TGF-β1) in plasma. (B) The level of tumor necrosis factor alpha (TNF-α) in plasma. Each group's data was collected from five rats.</p

The plasma concentration versus time curve (AUC) of 5-FU post irradiation was reversed by the matrix metalloproteinase-8 (MMP-8) inhibitor.

<p>The area under the plasma concentration versus time curve (AUC) of 5-FU 100 mg/kg administered to rats in the control group without solvent, control group with solvent, whole pelvic 2-Gy irradiation with solvent, and whole pelvic 2-Gy irradiation with solvent and MMP-8 inhibitor. The transverse axis illustrates time in minutes and the vertical axis represents the concentration of 5-FU in the plasma. Each group's data was collected from four rats.</p

Diarrhea score after administrating probiotics (<i>Lcr35</i> or <i>LaBi</i>) with/without 5-FU treatment.

<p>The mice were recorded daily and the results of all groups were compared with those in 5-FU + saline group for 5 days. In the control groups, the mice injected saline and administrated with saline (○), <i>Lcr35</i> (□) and <i>LaBi</i> (△). In the experimental groups, the mice injected 5-FU and administrated with saline (●), <i>Lcr</i> (■) and <i>LaBi</i> (▲). The severity of diarrhea was attenuated in those mice treated with probiotics in the 5-FU groups. The data with different superscripted letters are significantly different based on the one-way ANOVA.</p

Up-regulations of IL-6, IL-1β and TNF-α in mucositis mice were followed after injection with 5-FU.

<p>Mucositis mice were fed with (+) or without (−) probiotics. Gene expressions of IL-6, IL-1β and TNF-α were determined by Q-PCR (A) jejunum tissue (B) colon tissue. Induction of cytokine expressions were presented as RQ compared to 18sRNA housekeeping gene expression. The data with different superscripted letters are significantly different based on the one-way ANOVA.</p

A: Representative histology of jejunum showing villus height and crypt depth with haematoxylin and eosin stain in mice on day 5 challenged with 5-FU (IP). They were fed with probiotics (<i>Lcr35</i> or <i>LaBi</i>) or saline. The image acquisition phase was done with a 20x magnification objective. Scale bar = 200μm. B: Values were represented as mean ± SEM and were analyzed using one-way ANOVA. Segments of jejunum were taken for measurement of villus height, crypt depth and villus/crypt ratio per mouse.

<p>A: Representative histology of jejunum showing villus height and crypt depth with haematoxylin and eosin stain in mice on day 5 challenged with 5-FU (IP). They were fed with probiotics (<i>Lcr35</i> or <i>LaBi</i>) or saline. The image acquisition phase was done with a 20x magnification objective. Scale bar = 200μm. B: Values were represented as mean ± SEM and were analyzed using one-way ANOVA. Segments of jejunum were taken for measurement of villus height, crypt depth and villus/crypt ratio per mouse.</p

A: Representative histological sections of jejunum showing the goblet cells with haematoxylin and eosin stain in mice on day 5 challenged with 5-FU (IP). They were fed with probiotics (<i>Lcr35</i> or <i>LaBi</i>) or saline. The arrows indicated goblet cells. The image acquisition phase was done with a 20x magnification objective. Scale bar = 50μm. B: Jejunal goblet cells after staining were counted. Values were represented as mean ± SEM and were analyzed using one-way ANOVA.

<p>A: Representative histological sections of jejunum showing the goblet cells with haematoxylin and eosin stain in mice on day 5 challenged with 5-FU (IP). They were fed with probiotics (<i>Lcr35</i> or <i>LaBi</i>) or saline. The arrows indicated goblet cells. The image acquisition phase was done with a 20x magnification objective. Scale bar = 50μm. B: Jejunal goblet cells after staining were counted. Values were represented as mean ± SEM and were analyzed using one-way ANOVA.</p

Daily body weight change in percentage of saline or 5-FU-injected mice with/without probiotics (<i>Lcr35</i> or <i>LaBi</i>) administration.

<p>The mice were weighted daily and the results of all groups were compared with those in 5-FU-saline groups for 5 days. In the control groups, the mice were injected saline and administrated with saline (○), <i>Lcr35</i> (□) and <i>LaBi</i> (△). In the experimental groups, the mice were injected 5-FU and administrated with saline (●), <i>Lcr35</i> (■) and <i>LaBi</i> (▲). Data of starting bodyweight are expressed 100% from day 0.</p