Table 2.
Biomarkers for 5FU-induced AT toxicity and injury
| Animal | Protocol | Observations | Ref |
|---|---|---|---|
| mice | 450 mg 4FU/kg BW; ip; single dose | Significant damage, MPO activity and elevated levels of pro-inflammatory cytokines (IL-4, TNF-alpha, IL-1beta and CXCL-8) in the intestinal epithelium of 5FU-treated IL-4 wild-type mice but not in −/− mice | 94 |
| mice | 600 mg 5FU/kg BW; ip; single dose | Hg signaling consistently downregulated following 5FU during the injury phase followed by upregulation during the repair phase. Hg signaling inhibition augments apoptosis and suppresses mitotic activity in intestinal crypts | 95 |
| mice | 100 mg 5FU/kg BW; ip; single dose | Network analysis of 5FU-affected genes by transcriptomic tool shows that NF-kappaB is key molecule. 5-ASA inhibits 5FU-induced NF-kappaB activation and proinflammatory cytokine production | 88 |
| mice | 450 mg 5FU/kg BW; ip; single dose | In PAF-R −/− mice and PAF-R antagonist-treated mice, 5FU-induced intestinal damage is less than in wild-type mice | 96 |
| mice | 40 mg 5FU/kg BW; ip; single dose | IL-6 −/− mice exhibit increased apoptosis after 5FU relative to wild-type controls | 97 |
| rats | 50 mg 5FU/kg BW; iv; daily for 6 days | Increased plasma endotoxin,TNF-alpha and IL-6 levels in the 5FU animals. BT at liver, spleen, mesenteric lymph node, and portal blood | 98 |
| mice | 10 mg 5FU/kg BW; continuous iv infusion for 5 days | Reduced CD4/CD8 ratio in the lamina propria, GALT cell number and mucosal IgA levels after 5FU-exposure | 99 |
| rats | 30 or 60 mg 5FU/kg BW; orally; daily for 4 days | Higher Na+/K+-ATPase activity and D-glucose absorption in 5FU-treated rats | 100 |
| hamsters | 60 mg 5FU/kg BW; ip; on days 0, 5, and 10 | Decreases in cheek pouch and jejunum epithelium proliferation rates, increases in MMP-2 and -9, and plasmin, and decreases in TIMP-1 and -2 following 5FU | 101 |
| mice | 400 mg 5FU/kg BW; ip; 6 h between 2 injections | Reduced apoptosis in MBD4 −/− mice following treatment with gamma-irradiation, cisplatin, temozolomide and 5FU | 102 |
| mice | [14C] 5FU for 1 h at a flow rate of 20 ml/kg BW | 5FU induces apoptosis and/or cell cycle arrest: p21(WAF/Cip1)-positive nuclei migrate up the crypt, while bax-positive cytoplasm are observed throughout the crypt epithelial cells | 103 |
| mice | 40 mg 5FU/kg BW; ip; single dose | bcl-w −/− mice exhibit more apoptosis in the small intestine than the wild-type mice after 5FU-exposure | 104 |
| mice | 40 mg 5FU/kg BW; ip; single dose | Elevated apoptosis at base of crypts in colonic epithelium of 5FU-treated bcl-2 −/− mice. Bcl-2 seems to play a key role in determining the sensitivity of colonic stem cells to 5FU-damage | 105 |
| rats | 15 or 30 mg 5FU/kg BW, orally; daily for 3-4 days | BW loss and epithelial barrier dysfunction of the small intestine in 5FU-treated rats as shown by increased permeation of fluorescein isothiocyanate-labelled dextran | 106 |
| mice | 40 and 400 mg 5FU/kg; ip; single dose | Less 5FU-induced apoptosis and cell cycle inhibition in p53 −/− mice. | 107 |
| rats | 300 mg 5FU/kg BW; intragastrically; single dose | Reduced levels of glucose, phosphate transporter, sucrase and SGLT1 after 5FU-exposure | 108 |
| mice | 200 mg 5FU/kg BW; iv; single dose | Increase in adherence of C. albicans to murine GI mucosa after 5FU | 56 |