l-arginine minimizes immunosuppression and prothrombin time and enhances the genotoxicity of 5-fluorouracil in rats.

OBJECTIVE: The aim of this study was to evaluate the effect of low doses of l-arginine supplementation on hemogram, integrity of DNA and spleen, inflammatory infiltrate in the jejunum, and in the coagulogram of rats submitted to 5-fluorouracil (5-FU) chemotherapy. METHODS: Thirty-two Wistar rats were fed commercial feed and water ad libitum and grouped into four (eight rats per group): The control group was given a 0.9% physiologic solution to simulate the application of 5-FU in the other groups; the G5-FU group was given a dose of 5-FU; the GArg50 and GArg100 groups were given a dose of 5-FU and supplemented with 50 and 100 mg l-arginine/d added in the drinking water ad libitum. RESULTS: The rats in the GArg50 group did not lose weight after chemotherapy. GArg50 rats presented polycythemia owing to dehydration caused by diarrhea generated by 5-FU. GArg100 rats had increased total leukocyte count, eosinophils, lymphocytes, and index in the total index of DNA damage, yet showed a reduction in prothrombin time and in the spleen depletion index. Rats in the G5-FU, GArg50, and GArg100 groups had similar moderate inflammatory infiltrate in the jejunum. CONCLUSION: Supplementation with 100 mg/d of l-arginine minimized immunosuppression, spleen depletion, and prothrombin time and contributed to the breakdown of 5-FU-generated DNA in Wistar rats. Supplementation with 50 mg/d of l-arginine decreased the weight loss generated by 5-FU in Wistar rats. Supplements with 50 or 100 mg of l-arginine did not interfere with 5-FU-generated jejunal inflammatory infiltrate.

Effects of L-Arginine Supplementation on Leukogram, Inflammatory Bowel Infiltrates and Immunoglobulins with 5-FU Use in Rats.

This study evaluated the effects of L-arginine supplementation on blood parameters, kidney and liver function, immunoglobulins and noninflammatory infiltrates in the small intestines of rats subjected to chemotherapy with 5-fluorouracil (5-FU). Thirty-two Wistar rats were randomly distributed into 4 groups (8 rats/group): an untreated control group, and test groups receiving one dose of 5-FU (G5-FU group), one dose of 5-FU and 295 mg L-arginine/day (GArg295 group) or one dose of 5-FU and 458 mg L-arginine/day (GArg458 group). Neutrophil count, platelet count, serum IgA, and fibrinogen levels in GArg295 and GArg458 remained within normal limits after chemotherapy. In addition, in GArg458 the inflammatory bowel infiltrates improved in 57% of the rats, which showed mild inflammation. The results suggest that daily supplementation with 295 or 458 mg L-arginine attenuates the side effects of 5-FU, including thrombocytopenia and neutropenia, and modulates IgA production. Supplementation with 458 mg of L-arginine/day can also reduce mucositis levels in the small intestine after 5-FU chemotherapy.