title: Analysis of the oxidative damage of DNA, RNA, and their metabolites induced by hyperglycemia and related nephropathy in Sprague Dawley rats.
abstract: We used a sensitive and accurate method based on isotope dilution high-performance liquid chromatography-triple quadrupole mass spectrometry (ID-LC-MS/MS) to determine the levels of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosin (8-oxo-Gsn) in various tissue specimens, plasma, and urine of hyperglycemic Sprague Dawley rats induced by streptozotocin (STZ). The oxidative DNA and RNA damages were observed in various organs and the amounts of 8-oxo-dGsn and 8-oxo-Gsn derived from DNA and RNA were increased with hyperglycemic status. In contrast to the results of the nucleic acid samples derived from tissues, the levels of 8-oxo-Gsn in urine and plasma were significantly higher compared with that of 8-oxo-dGsn, which most likely reflected the RNA damage that occurs more frequently compared with DNA damage. For the oxidative stress induced by hyperglycemia, 8-oxo-Gsn in urine may be a sensitive biomarker on the basis of the results in urine, plasma, and tissues. In addition, high levels of urinary 8-oxo-Gsn were observed before diabetic microvascular complications. Based on that the 8-oxo-dGsn was associated with diabetic nephropathy and RNA was more vulnerable to oxidative stress compared with DNA. We also propose that 8-oxo-Gsn is correlated with diabetic nephropathy and that 8-oxo-Gsn in urine could be a useful and sensitive marker of diabetic nephropathy.
authors.affiliation: a Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College , Dongdan, Beijing , China.
authors.forename: Wan-Xia
authors.initials: WX
authors.lastname: Wang
authors.forename: Shun-Bin
authors.initials: SB
authors.lastname: Luo
authors.forename: Meng-Ming
authors.initials: MM
authors.lastname: Xia
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Mao
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Jiang
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Dai
authors.forename: Chuan-Bao
authors.initials: CB
authors.lastname: Li
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
mesh_terms: D000818:Animals; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D018384:Oxidative Stress; D012313:RNA / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
chemical_list: D015415:Biomarkers; C024829:8-hydroxyguanine; D013311:Streptozocin; D006147:Guanine; D012313:RNA; D004247:DNA
keywords: 8-oxo-7,8-dihydroguanosin; ID-LC–MS/MS; biomarker; guanosine; hyperglycemia