Renal excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine: degradation rates of RNA and metabolic rate in humans

Topp, Heinrich; Armbrust, S.; Lengger, Christoph; Schöch, G.; Davies, Joanne; Stichler, Willibald; Manz, Friedrich; Fusch, Christoph

doi:10.1016/s0003-9861(02)00034-6

Cited by 9 publications

(22 citation statements)

References 42 publications

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“…This further supports the hypothesis that rates of degradation of RNA are potential indicators of RMR, at least in healthy subjects [3,5]. If this is true, then RNA degradation rates or renally excreted modified RNA catabolites, especially the ribonucleoside ψ, may be regarded as new candidates for normalizing other metabolites in (-spot) urine samples to these indicators of metabolically active body mass and of its steadystate activity [3,5]. However, the above findings were obtained using exact 24 h urine samples or approximate 24 h urine samples with known collection times.…”

Section: Introductionsupporting

confidence: 83%

“…As further proof that rates of degradation of RNA are highly correlated with RMR, we have recently confirmed that whole-body degradation rates of tRNA and rRNA per kg lean body mass (LBM) are also highly correlated (r = 0.867 and r = 0.959 respectively) with measured RMR/LBM (RMR measured by indirect calorimetry and LBM by dual-energy X-ray absorptiometry) [5]. This further supports the hypothesis that rates of degradation of RNA are potential indicators of RMR, at least in healthy subjects [3,5].…”

Section: Introductionsupporting

confidence: 57%

“…Whole per kg LBM [5]. Therefore we postulated that rates of degradation of rRNA and tRNA may be novel indicators of the RMR of the LBM, and that the modified RNA catabolites ψ, m 2 2 G and t 6 A may be novel references for other metabolites in spot urine samples [3,5].…”

Section: Table 2 Diurnal Variations In the Calculated Whole-body Ratementioning

confidence: 99%

“…Therefore we postulated that rates of degradation of rRNA and tRNA may be novel indicators of the RMR of the LBM, and that the modified RNA catabolites ψ, m 2 2 G and t 6 A may be novel references for other metabolites in spot urine samples [3,5]. This is of interest when other metabolic products in urine, such as oxo 8 dG (8-oxo-7,8-dihydro-2 -deoxyguanosine; a marker of oxidative DNA damage by reactive oxygen species), can be related to metabolically active tissue and its RMR [5].…”

Section: Table 2 Diurnal Variations In the Calculated Whole-body Ratementioning

confidence: 99%

“…In various mammalian species, ranging in body weight over four orders of magnitude (from mouse to pig), as well as in children and adults, the whole-body rates of degradation of tRNA and rRNA were found to be highly correlated with the resting metabolic rate (RMR) [2][3][4][5]. In most of our previous studies, RMR was calculated using body weight and published empirical formulae [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Diurnal variation in the renal excretion of modified RNA catabolites in humans

Topp

Unverzagt²,

Rudloff

et al. 2003

Clinical Science

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Renally excreted modified RNA catabolites [pseudouridine (psi), N (2), N (2)-dimethylguanosine (m(2)(2)G) and N (6)-threoninocarbonyladenosine (t(6)A)] are markers of whole-body rates of degradation of rRNA and tRNA, and are thought to be potential indicators of the resting metabolic rate. To investigate diurnal variations of these RNA catabolites, the amounts of psi, m(2)(2)G and t(6)A excreted were determined by HPLC of the urine from eight healthy male adults collected over 47-h periods, which were subdivided into the morning (06.00 or 09.00 to 12.00 hours), the afternoon (12.00 to 18.00 hours), the evening (18.00 to 24.00 hours) and the night (00.00 to 06.00 or 08.00 hours), under two different nutritional regimens with 100 or 50 g of protein/day. Furthermore, rates of degradation of rRNA and tRNA were calculated using values for these RNA catabolites. For comparison, the corresponding excretion of creatinine, which originates from the energy metabolism of muscle, and of 3-methylhistidine (m(3)His), which is an indicator of muscle protein degradation, was determined. Differences in excretion during the collection periods were tested using the Friedmann test. The excretion of psi, creatinine and m(3)His (micromol x h(-1) x kg(-1)) altered significantly (P <0.001) during the day. Medians were: for psi, 0.21 (morning), 0.19 (afternoon), 0.19 (evening) and 0.18 (night); for creatinine, 8.8, 8.4, 8.0 and 7.3 respectively; for m(3)His, 0.13, 0.11, 0.12 and 0.10 respectively. The excretion rates of m(2)(2)G and t(6)A (nmol x h(-1) x kg(-1)) altered, but not significantly, during the day; corresponding medians were: for m(2)(2)G, 9.0, 8.4, 8.0 and 8.4 respectively; for t(6)A, 4.3, 4.1, 3.9 and 3.9 respectively. From these results it can be concluded that, in order to assess the average daily rates of degradation of tRNA and rRNA using modified RNA catabolites, urine collection should be carried out quantitatively over 24 h periods. Likewise, the catabolites creatinine and m(3)His must be determined using 24 h urine samples when average daily excretion values are required.

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