1. Early Supplementation of d-Cysteine or l-Cysteine Prevents Hypertension and Kidney Damage in Spontaneously Hypertensive Rats Exposed to High-Salt Intake
Chien-Ning Hsu, You-Lin Tain, Yu-Ju Lin, Pei-Chen Lu Mol Nutr Food Res . 2018 Jan;62(2). doi: 10.1002/mnfr.201700596.
Scope:We investigate whether early supplementation of precursors of hydrogen sulfide (H2S), d- or l-cysteine can prevent hypertension and kidney damage in spontaneously hypertensive rats (SHR) treated with high-salt.Methods and results:We examine 12-week-old male SHRs from four groups: SHR, high salt SHR (SHRs received 1% NaCl in drinking water for 8 weeks), high salt SHR+d (SHRs received high salt and d-cysteine), and high salt SHR+l (SHRs received high salt and l-cysteine). d- or l-cysteine was supplemented at 8 mmol kg-1body weight/day between 4 and 6 weeks of ages. High salt intake exacerbate hypertension and kidney damage in SHRs, which is prevented by d- or l-cysteine supplementation. d- or l-Cysteine supplementation reduce the degree of high salt-induced oxidative stress damage. Renal 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and activity are reduced by d- or l-cysteine supplementation. Additionally, d- or l-Cysteine supplementation reduce renal angiotensin I and angiotensin II concentrations, decrease mRNA expression of Ren, and increase protein levels of type 2 angiotensin II receptor.Conclusion:Early supplementation of d- or l-cysteine before hypertension becomes evident and may protect against hypertension and kidney damage in adult SHRs exposed to high salt consumption via regulation of oxidative stress, renin-angiotensin system, and H2S-generating pathways.
2. 18F-Trifluoromethylated D-Cysteine as a Promising New PET Tracer for Glioma Imaging: Comparative Analysis With MRI and Histopathology in Orthotopic C6 Models
Zhanwen Zhang, Shaoyu Liu, Dingxiang Xie, Jing Zhao, Dahong Nie, Hui Ma, Ganghua Tang, Zhiyun Yang, Fuhua Wen Front Oncol . 2021 Apr 29;11:645162. doi: 10.3389/fonc.2021.645162.
Comparing MRI and histopathology, this study aims to comprehensively explore the potential application of18F-trifluoromethylated D-cysteine (S-[18F]CF3-D-CYS) in evaluating glioma by using orthotopic C6 glioma models. Sprague-Dawley (SD) rats (n= 9) were implanted with C6 glioma cells. Tumor growth was monitored every week by multiparameter MRI [including dynamic contrast-enhanced MRI (DCE-MRI)], [18F]FDG,S-[18F]CF3-D-CYS, and [18F]FDOPA PET imaging. Repeated scans of the same rat with the two or three [18F]-labeled radiotracers were investigated. Initial regions of interest were manually delineated on T2WI and set on the same level of PET images, and tumor-to-normal brain uptake ratios (TNRs) were calculated to semiquantitatively assess the tracer accumulation in the tumor. The tumor volume in PET and histopathology was calculated. HE and Ki67 immunohistochemical staining were further performed. The correlations between the uptake ofS-[18F]CF3-D-CYS and Ki67 were analyzed. DynamicS-[18F]CF3-D-CYS PET imaging showed tumor uptake rapidly reached a peak, maintained plateau during 10-30 min after injection, then decreased slowly. Compared with [18F]FDG and [18F]FDOPA PET imaging,S-[18F]CF3-D-CYS PET demonstrated the highest TNRs (P< 0.05). There were no significant differences in the tumor volume measured onS-[18F]CF3-D-CYS PET or HE specimen. Furthermore, our results showed that the uptake ofS-[18F]CF3-D-CYS was significantly positively correlated with tumor Ki67, and the poor accumulatedS-[18F]CF3-D-CYS was consistent with tumor hemorrhage. There was no significant correlation between theS-[18F]CF3-D-CYS uptakes and the Ktransvalues derived from DCE-MRI. In comparison with MRI and histopathology,S-[18F]CF3-D-CYS PET performs well in the diagnosis and evaluation of glioma.S-[18F]CF3-D-CYS PET may serve as a valuable tool in the clinical management of gliomas.
3. Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase
Nayara A Sousa, Luan Kelves M Souza, Thiago S L Araújo, Kerolayne M Nogueira, Francisca Beatriz M Sousa, Jand Venes R Medeiros, Lucas A D Nicolau Nitric Oxide . 2017 Apr 1;64:1-6. doi: 10.1016/j.niox.2017.01.010.
Hydrogen sulfide (H2S) is a signaling molecule in the gastrointestinal tract. H2S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H2S to specific tissues. This study was designed to evaluate the concentration and effects of H2S (generated by d-amino acid oxidase [DAO] from d-cysteine) in the gastric mucosa and the protective effects against ethanol-induced lesions in mice. Mice were treated with l-cysteine or d-cysteine (100 mg/kg per os). Other groups received oral l-propargylglycine (cystathionine γ-lyase inhibitor, 100 mg/kg) or indole-2-carboxylate (DAO inhibitor), and 30 min later, received d- or l-cysteine. After 30 min, 50% ethanol (2.5 mL/kg, per os) was administered. After 1 h, the mice were euthanized and their stomachs excised and analyzed. Pretreatment with either l-cysteine or d-cysteine significantly reduced ethanol-induced lesions. Pretreatment of d-cysteine- or l-cysteine-treated groups with indole-2-carboxylate reversed the gastroprotective effects of d-cysteine but not l-cysteine. Histological analysis revealed that pretreatment with d-cysteine decreased hemorrhagic damage, edema, and the loss of the epithelium, whereas the administration of indole-2-carboxylate reversed these effects. d-Cysteine also reduced malondialdehyde levels but maintained the levels of reduced glutathione. Furthermore, pretreatment with d-cysteine increased the synthesis of H2S. Thus, an H2S-generating pathway (involving d-cysteine and DAO) is present in the gastric mucosa and protects this tissue from ethanol-induced damage by decreasing direct oxidative damage.