ORIGINAL ARTICLE Food Science and Technology Hepatoprotective action of dietary bluefin tuna skin proteins on CCl 4 -intoxicated mice Teruyoshi Tanaka • Kenji Takahashi • Naoki Iwamoto • Yasuo Agawa • Yoshifumi Sawada • Yukihiro Yoshimura • Nobuhiro Zaima • Tatsuya Moriyama • Yukio Kawamura Received: 13 January 2012 / Accepted: 2 April 2012 / Published online: 24 April 2012 Ó The Japanese Society of Fisheries Science 2012 Abstract We have shown that dietary bluefin tuna skin (TUS) protects against carbon tetrachloride (CCl 4 )-induced hepatic damage in mice. The CCl 4 -induced necrotic area was decreased in mice fed a TUS-containing diet. Con- sistent with the decreased necrotic area, dietary TUS markedly lowered the elevated serum aspartate amino- transferase (AST) and alanine aminotransferase (ALT) activities and the thiobarbituric acid-reactive substance (TBARS) formation induced by CCl 4 injection. TUS diets also decreased phosphorylation of inhibitory kappa B-a and blocked the translocation of nuclear factor-kappa B to the nucleus. TUS is composed mainly (80.7 %) of type I col- lagen, and our results revealed that dietary tuna collagen peptides (TUCP) attenuated the increased hepatic necrotic area, serum AST and ALT activities, and liver TBARS levels induced by CCl 4 , similar to TUS, thus enabling us to attribute the hepatoprotective action of TUS in CCl 4 - intoxicated mice to tuna collagen. Therefore, TUS and TUCP may be potential food resources that are capable of alleviating hepatitis symptoms. Keywords Bluefin tuna Á Skin proteins Á Collagen Á Hepatitis Á Carbon tetrachloride Introduction In 2002, the first full-cycle aquaculture of bluefin tuna was successfully performed at Kinki University, Japan. Cur- rently, more than 40,000 cultured bluefin tunas are avail- able from the bioventure company A-Marine Kindai (Wakayama, Japan). This increased supply of bluefin tuna has triggered research into the effective use of the unused parts of the tuna, such as its skin and organs, to avoid environmental pollution and promote economical effi- ciency. Therefore, the study described in this paper focused on bluefin tuna skin (TUS) as a collagen-rich, underused resource for functional food. Collagen is a major structural protein that is widely distributed in animal connective tissue. The unique primary structure of collagen bears a glycine-rich repeat sequence (Gly-X-Y), in which the presence of prolyl and hydrox- yprolyl residues at the X and Y positions configures the triple-helical structure [1, 2]. This biased amino acid composition has led past researchers to believe that colla- gen is not a nutritionally beneficial protein resource. Recently, studies related to the physiological functions of collagen and collagen peptides have been reported. Examples of these include the isolation of angiotensin I-converting enzyme-inhibitory peptides from chicken collagen hydrolysates [3, 4], and the finding that dietary collagen hydrolysates improved not only bone formation but also bone resorption in ovariectomized mice [5]. In addition, collagen-derived hydroxyproline-containing pep- tides such as Pro-Hyp, Pro-Hyp-Gly, and Leu-Hyp and free Pro and Hyp were also detected in human blood following the ingestion of collagen peptides [6]. Collagen is ubiquitously present in various animals with high homology. However, little is known about the phys- iological functions of dietary marine collagen compared to T. Tanaka Á K. Takahashi Á N. Iwamoto Á Y. Yoshimura Á N. Zaima Á T. Moriyama Á Y. Kawamura (&) Department of Applied Biological Chemistry, Graduate School of Agriculture, Kinki University, 3327-204, Naka-machi, Nara 631-8505, Japan e-mail: ykawamur@nara.kindai.ac.jp Y. Agawa Á Y. Sawada Ohshima Experiment Station, Fisheries Laboratories, Kinki University, 1790-4 Oshima, Kushimoto, Higashimuro, Wakayama 649-3633, Japan 123 Fish Sci (2012) 78:911–921 DOI 10.1007/s12562-012-0499-z