Plasma Thiols Levels in Alzheimer's Disease Mice under Diet-Induced Hyperhomocysteinemia: Effect of S-Adenosylmethionine and Superoxide-Dismutase Supplementation
Affiliations: [a] Istituto di Biochimica e Biochimica Clinica, Universitá Cattolica del Sacro Cuore, Rome, Italy | [b] Department of Surgery “P. Valdoni”, Sapienza University of Rome, Rome, Italy | [c] Department of Psychology, Section of Neuroscience, Sapienza University of Rome, Rome, Italy | [d] European Center for Brain Research (CERC)/IRCCS Santa Lucia Foundation, Rome, Italy | [e] Istituto di Chimica del Riconoscimento Molecolare – UOS Roma, Consiglio Nazionale delle Ricerche c/o Istituto di Biochimica e Biochimica Clinica, Universitá Cattolica del Sacro Cuore, Rome, Italy | [f] Centro di Ricerca in Biochimica e Nutrizione dello Sport (CriBeNS), Universitá Cattolica del Sacro Cuore, Milano, Italy
Correspondence:
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Correspondence to: Rosaria A. Cavallaro, Department of Surgery “P. Valdoni”, Sapienza University of Rome, via Antonio Scarpa, 14-00161 Rome, Italy. Tel.: +39 0649766604; Fax: +39 0649766600; E-mail: rosaria.cavallaro@uniroma1.it.
Abstract: Widely confirmed reports were published on association between hyperhomocysteinemia, B vitamin deficiency, oxidative stress, and amyloid-β in Alzheimer's disease (AD). Homocysteine, cysteine, cysteinylglycine and glutathione are metabolically interrelated thiols that may be potential indicators of health status and disease risk; they all participate in the metabolic pathway of homocysteine. Previous data obtained in one of our laboratories showed that B vitamin deficiency induced exacerbation of AD-like features in TgCRND8 AD mice; these effects were counteracted by S-adenosylmethionine (SAM) supplementation, through the modulation of DNA methylation and antioxidant pathways. Since the cellular response to oxidative stress typically involves alteration in thiols content, a rapid and sensitive HPLC method with fluorescence detection was here used to evaluate the effect of SAM and superoxide-dismutase (SOD) supplementation on thiols level in plasma, in TgCRND8 mice. The quantitative data obtained from HPLC analysis of mice plasma samples showed significant decrease of thiols level when the B vitamin deficient diet was supplemented with SAM + SOD and SOD alone, the latter showing the greatest effect. All these considerations point out the measurement of plasma thiols concentration as a powerful tool of relevance for all clinical purposes involving the evaluation of oxidative stress. The coupling of HPLC with fluorimetric detection, here used, provided a strong method sensitivity allowing thiols determination at very low levels.
