Combined Effects Of Adriamycin And Low-dose Radiation On Kidney Tissue Antioxidant Enzymes Of Nude Mice

Background and objective:Doxorubicin, as a core drug of chemotherapy, is limited to clinical applicationsowing to serious renal toxicity. Significantly reduce and control renal toxicity ofdoxorubicin is an important issue currently facing clinicians. Previous studies showedhormesis and adaptive response of low-dose radiation on normal cells rather thantumor cells. In vivo and in vitro experiments confirmed: low dose radiation does notreduce the efficacy of subsequent chemotherapy, while it can improve the tolerance tochemotherapy/radiotherapy and damage-repair capacity of normal tissue because ofits hormesis and adaptive responses. Based on these ideas, this study intends toinvestigate combined effects on animal models of low-dose radiation and doxorubicinon tumor growth and renal tissue antioxidant enzyme activity in the hope of low-doseradiation used in doxorubicin chemotherapy as an adjunct therapy of renal protection.Method:Breast cancer-bearing nude mice models was constructed and six experimentalgroups were set up: normal control group, sham-irradiated group, LDR group, LDR+ADM group [LDR+ADM(6h)；LDR+ADM(12h)], ADM group. Measure and recordthe growth and weight of transplanted tumors and calculate tumor inhibition rate.Take fresh kidney tissue homogenate, ELISA assay of SOD, GSH-Px activity assay,thiobarbituric acid (TBA) assay of MDA content.The experimental data is expressed asx±s. Groups were compared usingANOVA.Result:1. Compared with sham-irradiated group, the mean tumor weights weredecreased apparently in each group (P<0.05). LDR+ADM group showed thelowest mean tumor weight, but had no significant differences compared toLDR group and ADM group (P>0.05). The tumor inhibitory rate in LDR+ ADM group was significantly higher than that in ADM group and LDRgroup (P<0.05).2. Compare to normal control group, the value of SOD and GSH-Px weresignificantly decreased and the value of MDA was significantly increased insham-irradiated group (P<0.05).3. Compared with the sham-irradiated group, the value of SOD, GSH-Px inADM group were decreased, while those in LDR group were increased; thevalue of MDA in ADM group was increased while that in LDR group wasdecreased (P<0.05).4. Compared to ADM group, the value of SOD and GSH-Px were increasedand the value of MDA were decreased in LDR+ADM group (P<0.05).Conclusion:1. LDR does not produce hormesis and adaptive response in breast cancer. Itmay produce a synergistic antitumor effect combined with doxorubicin.【LDR does not promote tumor growth but has some inhibition effect to thetumor of nude mice bearing breast cancer. The tumor inhibition effect can beenhanced by a synergistic antitumor effect when LDR combined withadriamycin.】2. LDR can enhance the antioxidant enzyme activity in kidney tissue of breasttumor-bearing mouse, and reduce lipid peroxidation formation producing,thereby inhibiting oxidative stress reaction to reducing doxorubicin-inducedkidney injury.