Anti-oxidant vitamins reduce normal tissue toxicity induced by radio-immunotherapy

Abstract

Our purpose was to determine whether the administration of anti‐oxidant vitamins could reduce dose‐limiting toxicity from radio‐immunotherapy (RAIT) and thereby allow higher escalation of RAIT doses. Lipophilic vitamins A and E were administered i.p. and hydrophilic vitamin C was administered i.m. for 14 days (3 days pre‐RAIT through 11 days post‐RAIT) alone or with bone marrow transplantation (BMT) to either BALB/c mice for toxicity studies or to nude mice bearing s.c. GW‐39 human colonic cancer xenografts for therapy studies. The maximal tolerated dose (MTD) of RAIT (131I‐MN14 anti‐CEA IgG) that results in no lethality was determined for mice that did not receive vitamins or BMT and those that did receive one or both interventions. Body weight, peripheral white blood cell (pWBC) and platelet (PLT) counts and tumor growth were also measured. Administration of vitamins (equivalent of 3.5 IU/day vitamin A, 0.107 IU/day vitamin E and 4.0 mg/day ascorbic acid) to mice along with BMT increased the MTD by 42% and reduced body weight loss associated with RAIT. Vitamins also reduced the magnitude of RAIT‐induced myelosuppression. As early as day 7 after RAIT, vitamins increased WBC counts following both a 400 μCi and a 500 μCi dose. On day 14 after the 400 μCi dose of RAIT (day 7 post‐BMT), the additive effect of BMT and vitamin could be detected. Tumor growth was not adversely affected by vitamin administration. Int. J. Cancer 86:276–280, 2000. © 2000 Wiley‐Liss, Inc.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

“…Lipid peroxidation products increased with chemotherapy have been reported to decrease free radical scavengers antioxidant vitamins, such as vitamins A, E, and C 4,26 . In another in vivo and in vitro study, the use of vitamins E, A, and C against oxidative stress caused by chemotherapy has been found to enhance the therapeutic effect and also protect normal cells against apoptosis 5 . It has been reported in a cell culture and animal model that the combinations of vitamins A, B6, B12, C, D, and E with β-caroten protected against adverse effects of chemotherapy prolonged survival time and increased response to treatment 26 .…”

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

“…This finding is supported by the studies of Blumenthal et al , who found that a dietary supplement of vitamins A, C and E (administered in diet at 10× the daily requirement) increased the maximum tolerated dose of 131 I-labeled radiolabeled antibody administered to mice ( 131 I-MN-14) (10). Other studies have shown that antioxidant diet supplementation can be an effective treatment to reduce radiation death in rodents (47, 48).…”

“…Vitamin C and E supplements reduced bleeding and diarrhea in patients with chronic radiation proctitis due to previous pelvic irradiation (27). A combination of vitamins A, C and E reduced bone marrow toxicity caused by radioimmunotherapy with 131 I-labeled antibodies (10). Furthermore, we have demonstrated a diet enriched in vitamins A, C and E (vitamin ACE) protects intestinal transport of these nutrients under acute irradiation conditions (4).…”

Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion

“…Mixtures of radioprotectors offer a means to both improve DMF values and increase coverage with respect to the types of radiation damage that can be protected against. A combination of vitamins A, C and E reduced bone marrow toxicity caused by radioimmunotherapy with 131 I labeled antibodies (Blumenthal et al 2000) and prevented reductions in intestinal nutrient transport caused by whole-body acute and chronic irradiation (Roche et al 2011, Roche et al 2015). …”