Study On The Radiation Protective Effects Of Two Derivatives Of The L-cysteine And The Mechanisms

Objective With the wide promotion and utilisation of the nuclear technology in military affairs, technology and medical treatment, the opportunities that people exposed to various rays increased. The possibility of suffering from radiation damage is also growing. Radiation can cause different types of acute and chronic radiation sickness, such as bone marrow, intestinal and cerebral radiation sickness. Disastrous consequences occur if not treated in time. Therefore, strengthening the treatment for the radiation sickness is always a hot and difficult problem in this field.Currently, there are many drugs available for radiation protection at home and abroad, like Traditional Chinese Medicine, hormones, antibiotics, vitamins, sulfhydryl compounds, disinfectant, etc. But one common property of these drugs is the severe side effect. Take the mercapto compounds amifostine for example, as adjuvant treatment of tumor radiotherapy and cytotoxic chemotherapy agent, it has good efficiency. However, since it has been listed, the causing side effects such as hypotension, vomiting, lethargy, sneezing, facial flushing limits it’s clinical application. This study is based on structural modification of the existing compounds and then8new comopounds were obtained. Further, the radiation protection activities of the new compounds were systematically evaluated and finally the mechanisms were also discussed.Methods The30-day survival rate was used to assess the radiation protection activities of the eight compounds. A compound (named isopentenyl-L-cysteine) with good protection activity was screened out. Then the protective effect of isopentenyl-L-cysteine against the oxidative damage caused by the gama ray irradiation was evaluated. Finally, the effects of isopentenyl-L-cysteine on DNA and hematopoietic system were also studied.1. Radiation protection activities of the eight new compounds in ICR mice:30-day survival rate, the average survival time, the protection index in irradiation injured mice were observed; Mice were given different doses of gama ray irradiation (6.5-8.5Gy) to deterine the value of dose reduction factor (DRF). 2. The effect of the isopentenyl-L-cysteine on hematopoietic system:To study the changes of peripheral blood cell blood and the index of hematopoietic system in mice after receiving a lethal dose and sublethal dose of the gama ray irradiation respectively.3. Observation of the protective effect of isopentenyl-L-cysteine against the oxidative damage induced by gama ray irradiation:To study the changes of MDA, GSH, SOD, CAT in liver, lung and blood after receiving a sublethal dose of the gama ray irradiation.4. Observation of the effect of isopentenyl-L-cysteine on DNA:The neutral single cell gel electrophoresis and bone marrow polychromatic micronucleus technique were used to evaluate the DNA breaks after receiving1.0and7.2Gy gama irradiation respectively.Result1. The survival time of isopentenyl-L-cysteine significantly increased compared with that of the control group. Survival rate in the group of isopentenyl-L-cysteine with high dose, compared with the control group, increased by45.14%, the protective index is1.4282. The double strand DNA broken in lymphocytes was obviously decreased when mice were preventively given isopentenyl-L-cysteine before irradiation. The percentage of TDNA, TL, TM and OTM had a significant decrease in the group of isopentenyl-L-cysteine. Meanwhile, a significant decrease in the rate of micronuclei in prevention group was also observed.3. The WBC, BMNC, CFU-S, Spleen index and thymus index had a significant increase in the group of isopentenyl-L-cysteine, especially in the middle dose group, after receiving a sub-lethal dose of y-ray irradiation, While there is not a significant difference in peripheral hemogram (WBC, RBC, Mon, Lymph, HGB, PLT, Gran, HCT) in the following30-day in lethally irradiated mice. 4. At the dose of6.5Gy, isopentenyl-L-cysteine could inhibit the decrease of T-SOD, GSH and CAT activities and increase of the amount of MDA to some extent, in the lung, liver and serμm after irradiation.Conclusion Isopentenyl-L-cysteine has protective effects on mice irradiated by137Cs y-ray. The mechanism might be attributed to its hematopoietic promoting capability and the protection of DNA. Further studies on the effect of the isopentenyl-L-cysteine on peripheral hemogram are needed.