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.

Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications

“…We also found that age had a significant effect on both 8-oxodGuo and 8-oxoGuo in the study subjects. This confirmed our previous research [ 18 , 19 ] and also the review by Jacob et al [ 20 ].…”

Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A Prospective Cohort Study

“…Sex-stratified Cox models did not indicate any change in the results. diabetes is supported by evidence from animal models, and 8-oxoGuo has been found to be a more sensitive nucleic acid marker of diabetes morbidity and mortality than 8-oxodG (28). Moreover, a cross-sectional study indicated notably higher 8-oxoGuo levels in patients with type 2 diabetes with diabetic macrovascular complications, as well as higher 8-oxodG levels (although to a lesser extent) (29).…”

“…A further strength of this study is the method used for quantifying RNA oxidation. On oxidation, RNA is degraded and the oxidized nucleoside is excreted into urine, which can be assessed and interpreted to reflect intracellular disturbances in metabolism (28). The measurement of the oxidative modified nucleoside ensures that it does not originate from intestinal absorption, thus minimizing the contribution of diet and bacterial breakdown (38,39).…”

A mathematical model as a tool to identify microRNAs with highest impact on transcriptome changes

“…The results reported here are consistent with the hypothesis that these rapid changes in mRNA expressions result, at least in part, from damage to miRNAs and mRNAs by ROS which leads to perturbation of their interactions. It is not generally recognized that RNA is even more sensitive than DNA to oxidative damage [49]; the effects of ROS on RNA have been less explored, but in HeLa cells exposed to sub-milimolar concentrations of H 2 O 2 for 1 h, they led to a 50% decrease in the level of 8-oxoG in total RNA (reviewed in [50]). In our top-ranked miRNAs which seem to influence mRNA expressions most, the seed region is significantly enriched in GC; G has the lowest ionizing potential of the nucleic acid bases and G-specific damage by ROS is well documented for DNA and is therefore likely for RNA [51].…”