Distribution of procyanidins and their metabolites in rat plasma and tissues after an acute intake of hazelnut extract† Aida Serra, a Alba Maci a, a Maria-Paz Romero, a Neus Angl  es, b Jos e Ram on Morell o b and Maria-Jos e Motilva * a Received 27th May 2011, Accepted 1st August 2011 DOI: 10.1039/c1fo10083a Procyanidins are present in a wide range of dietary foods and their metabolism is well known. Nevertheless, the biological target and their distribution are topics lacking information. The purpose of the present work was to study the metabolism and distribution of procyanidins and their metabolites in rat plasma and different tissues, such as liver, brain, lung, kidney, intestine, testicle, spleen, heart and thymus, after 2 h of an acute intake of hazelnut extract rich in procyanidins (5 g kg 1 of rat body weight). The interest of an acute intake of procyanidins instead of repeated low doses from daily ingestion of is to achieve a concentration of metabolites in the tissues that allows their detection and quantification. The results showed that catechin and epicatechin-glucuronide, methyl catechin and epicatechin-glucuronide and methyl catechin and epicatechin-sulphate were detected in plasma samples at the mmol level. On the other hand, catechin-glucuronide, methyl catechin-glucuronide and methyl catechin-sulphate were identified in some tissues, such as thymus, intestine, lung, kidney, spleen and testicle at the nmol level. Procyanidins with a low grade of polymerization (dimers and trimers) were detected in plasma samples and the intestine. Additionally, a wide range of simple aromatic acids from fermentation by the colonic microflora was detected in all tissues studied. 1 Introduction It is well known that polyphenols present in food are highly metabolized before their absorption. In recent years, attention has focused on the digestion and gastrointestinal metabolism of procyanidins. 1–6 Prior to absorption, procyanidins are hydro- lyzed by digestive enzymes or colonic microflora 7 and during the absorption step, procyanidins are conjugated in the small intes- tine, resulting in a wide range of conjugated metabolites, from the combination of sulphatation, glucuronidation and methyla- tion. 8–10 Additionally, the colonic microflora also participates in the last step of the procyanidin metabolism, generating new small molecules by hydrolysis, mainly simple aromatic acids. Secondly, procyanidins are metabolized by the liver where they can be modified into a variety of metabolites, mainly glucuronide conjugates. Throughout digestion, hydrolysis and metabolism change the molecular structure of procyanidins, leading to a large number of different molecules. These structural modifications may exert a negative influence on their biological activities, as occurs with the antioxidant activity, which decreases drastically when the hydroxyl group is modified. 6 Different studies have shown the bioavailability of procyanidins by studying the concentration of their metabolites in plasma and urine. 4,11–13 Nevertheless, deter- mination of the bioavailability of polyphenol metabolites in tissues may be much more important than knowledge of their plasma concentrations. 7 There is a lack of knowledge about the specific target organs where the metabolites derived from ingested procyanidins accu- mulate. The existing studies related to the distribution of pro- cyanidins in tissues focus on evaluating the behavior of a single molecule, such as epicatechin, by detecting this compound and its metabolites in some rat tissues. 6,14 However, it is well known that foods contain a complex mixture of phenolic compounds 6,14 making the study of metabolism, distribution and accumulation of procyanidins in the body more difficult. These are the reasons why we report in this paper on a comprehensive study of the absorption, metabolism and distribution in plasma and body tissues (thymus, heart, brain, spleen, testicle, intestine, kidney, lung and liver) of (+)-catechin and ()-epicatechin and procyanidins with a low degree of polymerization (dimers and trimers) following the oral intake of a high dose of hazelnut extract in rats (5 g kg 1 of rat body weight). To observe and understand the future potential benefits of polyphenols, taking into account their short life in plasma, the studies should be carried out during the postprandial state, immediately after ingestion. 15,16 So, the aim of an acute intake of a Department of Food Technology, XaRTA-UTPV, Escola T ecnica Superior d’Enginyeria Agr  aria, Universitat de Lleida, Avda/Alcalde Rovira Roure 191, 25198 Lleida, Spain. E-mail: motilva@tecal.udl.es; Fax: +34 973 702596; Tel: +34 973 702817 b R + D + i Department, La Morella Nuts, S.A., Cam ı Ample s/n, 43392 Castellvell del Camp, Spain † Electronic supplementary information (ESI) available: Optimized SRM conditions and concentration of metabolites in different tissues of rat control group and rat group after an acute intake of the nuts skin extract. See DOI: 10.1039/c1fo10083a 562 | Food Funct., 2011, 2, 562–568 This journal is ª The Royal Society of Chemistry 2011 Dynamic Article Links C < Food & Function Cite this: Food Funct., 2011, 2, 562 www.rsc.org/foodfunction PAPER Downloaded on 09 December 2011 Published on 05 September 2011 on http://pubs.rsc.org | doi:10.1039/C1FO10083A View Online / Journal Homepage / Table of Contents for this issue