Metabolic significance of bisphenol A-induced oxidative stress in rat urine measured by liquid chromatography-mass spectrometry

Modified nucleosides are formed by DNA repair as a result of oxidative DNA damage and post-transcriptionally modified tRNA in cells. In the present study, profiling of 14 nucleoside was investigated in rat urine to evaluate bisphenol A (BPA)-induced oxidative stress after intraperitoneally injecting rats with 0, 10 or 50 mg kg^-1 per day of BPA for four consecutive days. The urinary concentrations of individual nucleosides were measured by liquid chromatography-tandem mass spectrometry combined with column switching on-line extraction. Increased levels of 5-hydroxymethyl-2′-deoxyuridine (P < 0.01 on first, P < 0.005 on second, P < 0.001 on third and P < 0.01 on fourth day) and 8-hydroxy-2′-deoxyguanosine (P < 0.005 on second, P < 0.001 on third and P < 0.001 on fourth day) were found. Also, the patterns of urinary nucleosides in three dosage groups (control, BPA1, BPA2) were significantly different. Statistical significance was observed between BPA1 (5-hydroxymethyl-2′-deoxyuridine, P < 0.05; 8-hydroxy-2′- deoxyguanosine, P < 0.005) and BPA2 (5-hydroxymethyl-2′-deoxyurindine, P < 0.005; 8-hydroxy-2′-deoxyguanosine, P < 0.001) during the treatment period. Supervised analysis with partial least-squares-discrimination analysis led to discrimination between the three dosage groups. Quantitative alterations showed the metabolic trajectories responsible for physiological responses. The described methods could be used to evaluate and monitor BPA-induced oxidative stress early after exposure.