Urinary excretion of oxidative damage markers in a rat model of vascularized composite allotransplantation.
BACKGROUND
Vascularized composite allotransplantation is an emerging field of transplantation that provides a potential treatment for complex tissue defects after traumatic loss or tumor resection and for the repair of congenital abnormalities. However, vascularized composite allotransplantation recipients have suffered from acute and chronic graft rejection that is associated with oxidative stress. This study investigated the oxidative damage in a rat vascularized composite allotransplantation model by measuring three urinary biomarkers, 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and malondialdehyde.


METHODS
Rats received two different immunosuppressants, including cyclosporine A and mycophenolate mofetil after transplantation, with one group also receiving mesenchymal stem cells before transplantation. Urine was collected and analyzed for 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and malondialdehyde by liquid chromatography coupled to tandem mass spectometry methods.


RESULTS
Rats undergoing vascularized composite allotransplantation had higher urinary levels of 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and malondialdehyde compared with rats undergoing syngeneic transplantation. Cyclosporine A/mycophenolate mofetil following treatment prolonged the allograft survival in a dose-dependent manner. Compared with rats undergoing vascularized composite allotransplantation with cyclosporine A/mycophenolate mofetil treatment alone, rats undergoing mesenchymal stem cell combined treatment showed the longest allograft survival, and had approximately 50 percent lower urinary levels of malondialdehyde together with approximately 2.7-times higher levels of 8-oxo-7,8-dihydroguanine.


CONCLUSIONS
Mesenchymal stem cell combined treatment efficiently managed oxidative stress in rats undergoing vascularized composite allotransplantation, and urinary 8-oxo-7,8-dihydroguanine and malondialdehyde could be regarded as good responders to the mesenchymal stem cell therapy.
Taoyuan and Taichung, Taiwan From the Center for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung University; the Department of Public Health, Chung Shan Medical University; and the Department of Family and Community Medicine, Chung Shan Medical University Hospital.
Ching-Hsuan
CH
Hu
Cheng-Hung
CH
Lin
Nai-Jen
NJ
Chang
Chiung-Wen
CW
Hu
Chih-Hung
CH
Lin
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D006084:Graft Rejection / Q000188:drug therapy / Q000378:metabolism*; D006085:Graft Survival / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008315:Malondialdehyde / Q000652:urine; D059630:Mesenchymal Stem Cells / Q000166:cytology; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D063986:Vascularized Composite Allotransplantation / Q000379:methods*
D015415:Biomarkers; D007166:Immunosuppressive Agents; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine