Inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid, an acrolein-glutathione metabolite

• Published in: Clinica chimica acta Vol. 413; no. 7-8; pp. 753 - 759
• Main Authors: Yoshida, Madoka, Mikami, Takahiro, Higashi, Kyohei, Saiki, Ryotaro, Mizoi, Mutsumi, Fukuda, Kazumasa, Nakamura, Takao, Ishii, Itsuko, Nishimura, Kazuhiro, Toida, Toshihiko, Tomitori, Hideyuki, Kashiwagi, Keiko, Igarashi, Kazuei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 11.04.2012
• Subjects: 3-Hydroxypropyl mercapturic acid; Acetylcysteine - analogs & derivatives; Acetylcysteine - urine; Acrolein; Acrolein - metabolism; Adult; Aged; Case-Control Studies; Chromatography, Liquid; Female; Glutathione; Glutathione - metabolism; Humans; Male; Middle Aged; Polyamines; Stroke; Stroke - urine; Tandem Mass Spectrometry; Stroke; CH; CI; Polyamines; IL-6; Acrolein; SMO; 3-HPMA; Cre; ROS; PC-Acro; SBI; GSH; AcPAO; 3-Hydroxypropyl mercapturic acid; Glutathione
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2012.01.020

We found previously that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good biomarkers for stroke. The aim of this study was to test whether 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, was increased in the urine of stroke patients. The level of 3-HPMA in urine was measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Stroke (78 subjects) was divided into 52 cerebral infarction (CI) and 26 cerebral hemorrhage (CH) on the basis of clinical information including brain imaging. A major acrolein derivative in urine is 3-HPMA. Being different from the results of PC-Acro in plasma, 3-HPMA in urine decreased following stroke. The median value of μmol 3-HPMA/g creatinine (Cre) for 90 control subjects was 2.83, while that for 78 stroke patients was 1.56. The degree of the decrease in 3-HPMA was similar in both CI and CH patients. Furthermore, the median value of μmol 3-HPMA/g Cre in 56 patients with lesions ≥1cm in diameter (1.39) was significantly lower than that in 20 patients with lesion <1cm in diameter (2.16). Inverse correlation between stroke and urinary 3-HPMA was observed. The results suggest that stroke is aggravated when nervous system tissues have a reduced level of glutathione. ► 3-HPMA in urine, acrolein conjugate of GSH, decreased following stroke. ► Decrease in 3-HPMA was parallel with the size of infarction. ► The results suggest that stroke is aggravated when GSH in nervous tissues is low.