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

Abstract

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 G_5-FU group was given a dose of 5-FU; the G_Arg50 and G_Arg100 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 G_Arg50 group did not lose weight after chemotherapy. G_Arg50 rats presented polycythemia owing to dehydration caused by diarrhea generated by 5-FU. G_Arg100 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 G_5-FU, G_Arg50, and G_Arg100 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.

Keywords: arginine; cytotoxicity; drug therapy; immunologic; neoplasms.