| Objective: Chemotherapy is an important method for the treatment of cancer. Chemotherapeutic drug can cause some severe side effects. So it is urgent to prevent the drug adverse effects of chemotherapy. Some research in rencent years suggested that riboflavin has close relation with the prevention and therapy of tumour. Riboflavin is the efficient part of riboflavin laurate(RFL). As a constituent of two redox coenzymes, namely flavin mononucleotide(FMN) and flavin adenine dinucleotide(FAD), riboflavin takes part in complex oxidation-reduction process and has very important pharmacological effects. Here we study the protective effects of RFL preconditioning on rats gut mucositis after chemotherapy.Methods: 70 Wistar rats, weighing 210~250g, were randomly divided into four groups. Group A is normal control group(n=10), group B is methotrexate(MTX) control group(n=20), group C is RFL pretreatment group (RFL, n=20) , group D is RFL pretreatment and calcium folinate group (RFL+CF, n=20). All rats in group B~D were subcutaneously injected with the chemotherapeutic drug MTX(3.0mg/kg)on d 1, 2 and 3. RFL was infused with muscle at 24h before the first MTX injection. CF was subcutaneously injected at 24h after MTX injection for 3 times. Rats were killed at day 6,10 after MTX injection. In the first experiment, to explore methotrexate induced oral ulcers in rats, feed intake and body weight were measured daily. To observe the time of appearance and coalesced of oral ulcer, the graduation of oral ulcer and hemopoiesis repression. The second experiment was to explore intestinal mucositis of rats after chemotherapy. The changes of weight of small intestinal, villus surface length in the intestinal mucosa, small intestinal tissue morphology and ultra structure, the content of malondialdehyde(MDA), the activity of diamine oxidase(DAO) and glutathione peroxidase(GSH-Px ) were observed.Results: 1. The loss of body weight and appetite obviously decreased on d 3~8, reached anadir on d 5 or 6. Compared with the MTX control group, RFL group especially increased in the feed intake , body weight and decreased hemopoiesis repression of rats(P<0.05,P<0.01), the time of oral ulcer appearance was delayed and coalesced was early, the graduation was slight. There were no significant differences between the RFL+CF group and normal control group.2. Small bowel damage increased in severity up to d 6(72h after the third and final methotrexate injection) ,followed by rapid recovery such that most criteria had returned to normal by d 10. On d 6,compared with the MTX control group, RFL and RFL +CF obviously increased in the weight of small intestinal(P<0.05 ,P<0.01), the villus surface length(P<0.01), changes of small intestinal tissue morphology and ultra structure were slight. They also decreased the content of MDA, increased the activity of DAO and GSH-Px(P<0.05,P<0.01). Besides the villus surface length, there were no significant differences among the four groups on d 10. Conclusions: It was indicated that RFL was the scavenger of oxygen free radicals (OFR)and capable of prophylacticly antagonizing against the oxidative injury. It could increase the antioxidation of organism and efficaciously relieve the oral mucosa and the small bowel injury after chemotherapy, which suggested clinical applications for the treatment of gut mucositis. |
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