An Observation Of Toxic And Side Effect In Combination Of Immunosuppressive Agents On CIA Rat Model

Objective:To provide more basis of animal model for selection of treatment of lest toxic and side effect clinical therapy by observed and compared the collagenâ…¡conduced arthritis(CIA) rat which treated by CTX+LEF, CTX+MTX or LEF+MTX. Method:1. Rendomly pick up 60 rats to establish CIA rat mode, then take 45 success CIA rats and rendomly divided into 3 groups:group A(CTX+LEF), group B(CTX+MTX), group C(LEF+MTX), and pick up addisional 15 rats for bank group(normal saline), respectively administer treat each groups.2. Respectively test the side effect included blood urea nitrogen(BUN), serum creatinine(Scr), white blood cell count(WBC), red blood cell count(RBC), peripheral blood leucocyte(PLT), alanine aminotransferase(ALT) on 12th and comet assay for DNA damage of liver, kindney, marrow cell and peripheral blood leucocyte(PBL) on 24th week.Results:1.Comparation between treat groups and contorl group after administer show there are dramatically increase of alanine aminotransferase(ALT) and the legth of comet tail of liver cell, P<0.05; there are dramatically decrease of white blood cell count(WBC) and increase of legth of comet tail of peripheral blood leucocyte(PBL) and marrow cell both in group A and group B, P<0.05.2. There is dramatically joint effect on increasing legth of comet tail of PBL between CTX and MTX, P<0.05. Conclusion:1. All the three treatments:CTX+LEF, CTX+MTX and MTX+LEF will cause the damage on blood system and liver, but there is no significant damage on urinary tract.2. There is a joint effect on increasing DNA damage of PBL between CTX and MTX; 3. The decreasing of WBC may reflect on the damage from drugs of PBL DNA, ALT may not accurately reflect on the damage of DNA of liver cells.