Supplementation with L-Arginine Decreases Jejunal Lesions and Micronucleus Formation Induced by 5-Fluorouracil in Rats.

The objective of this study was to evaluate the effect of L-arginine supplementation on the formation of jejunal lesions and micronuclei in Wistar rats following 5-fluorouracil (5-FU) treatment. Fifty rats were separated into five groups: CG served as the control group, GArg was supplemented L-arginine, G5-FU was administered 5-FU, GArg+5-FU was supplemented L-arginine/day and administered 5-FU, and Gciclo served as a positive control group for micronuclei formation. Jejunal lesions were assessed by histopathological analysis using a scoring system with a maximum of 39 points, based on the following lesions: lymph vessel dilatation, cubic enterocytes, villous flattening, villus fusion, interstitial edema, and apical necrosis of the villi. Micronuclei were counted in polychromatic erythrocytes from the femur bone marrow. The control and GArg rats had the lowest number of jejunal lesions (6.4 ± 2.8 and 5.3 ± 2.4, respectively) and micronuclei (1.9 ± 0.6 and 1.1 ± 0.3, respectively) while the G5-FU rats had the highest number of jejunal lesions (24.2 ± 4.9) and micronuclei (36.0 ± 8.5). The GArg+5-FU rats showed significantly reduced (P < 0.05) jejunal lesions (10.2 ± 4.9) and micronuclei (15.4 ± 5.9). In conclusion L-arginine supplementation potentially reduces the jejunal lesions and DNA damage caused by 5-FU.

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.