International Dairy Journal 16 (2006) 1005–1012 Antiulcerative properties of bovine a-lactalbumin L.F.H. Mezzaroba, J.E. Carvalho, A.N. Ponezi, M.A. Antoˆ nio, K.M. Monteiro, A. Possenti, V.C. Sgarbieri State University of Campinas (Unicamp), Dept. Foods and Nutrition, Rua Monteiro Lobato, 80, CEP 13083-862, Campinas, SP, Brazil Received 20 April 2005; accepted 4 October 2005 Abstract The capacity of a-lactalbumin to protect the rat stomach mucosa against ulcerative lesions caused by indomethacin or a was investigated. An a-lactalbumin prepared in the laboratory by anion exchange and molecular exclusion chromatograph and a commercial a-lactalbumin (Comm.a-La) were compared with a saline control. Comm.a-La offered 44% protection ver La 12%, in the indomethacin model. For absolute ethanol, no statistical difference was found in the inhibition of the develo ulcerative lesions for the two a-lactalbumins, ranging from 32% to 50%. The content of prostaglandin E 2 (PGE 2 ) and mucus increased in the mucosa after a-La intubation, suggesting that the protein protects the mucosa via stimulation of PGE 2 and mucus production. Blocking free sulfhydryl groups by in vivo N-ethylmaleimide alkylation caused an increase in mucosal ulcerative lesions, su importance of sulfhydryl compounds in the gastric mucosa protection. r 2006 Elsevier Ltd. All rights reserved. Keywords: a-Lactalbumin; Ulcerogenesis; Indomethacin; Ethanol 1. Introduction a-Lactalbumin (a-La) has recently been associated with reduction of stress (Markus et al., 2000), immunomodula- tion (Montagne,Cuiliere,Mole, Bene,& Faure, 2000), antimicrobial activity (Pelligrini, Thomas, Bramaz, Hunzi- ker, & Fellenberg,1999; Pihlanto-Leppa ¨la¨etal., 1999), bactericidal and apoptotic activity ( Hakansson et al., 2000; Svensson,Hakansson,Mossberg,Linse, & Svanborg, 2000),and antiulceractivity (Matsumoto,Shimokawa, Yshida,Toida, & Hayasawa,2001; Ushida,Shimokawa, Matsumoto, Toida, & Hayasawa, 2003). In addition to its well known activity asenzymatic cofactor in mammary gland synthesisof lactose(Walstra, Geurts, Noomen, Jellema, & van Boekel, 1999). The gastric mucosa is among the most important tissues in the organism on account of its function, structure and pathological processes that can take place in it (Melo, Castro, Lanna, Guimara ˜es, & Sobrinho, 1993).It is accepted that the peptic ulcerogenesis (gastric and duode- nal) results from an imbalance between infectious agent like the bacteria Helicobacter pylori or aggressive chemic agents versus protectivesubstancessuch as mucus, bicarbonate, prostaglandins (PGE 2 and PGI 2 ), sulfhydryl compounds such as proteins, glutathione and others, as well as the blood flux to the mucosa cells ( Abdel-Salam, Czimmer,Debreceni, Szolesanyi, & Mo´zsik,2001; Allen, Flemstro ¨m, Garner, & Kivilaasko, 1993; Kontereck, 1993; Robert, 1979; Szabo, Nagy, & Pevebani, 1992). The mucu and bicarbonates are responsible for the formation of an immobile viscous layer that protects the mucosa from the action of hydrochloricacid (Allen et al., 1993).The bicarbonate ions bind to the mucus creating a pH gradien (pH 1–7) from the stomach interior to the mucosa surface The regulation of acid secretion by the HCl secreting cells is very important in the control of peptic ulcers. The acid secretion control is normally done by using H 2 receptor antagonists, inhibitors of proton pump and/or neutraliza- tion of the secreted acid using antacid substances ( Rang Dale, & Ritter, 1997). Sulfhydryl substances such as cysteine, glutathione, an others can protect the mucosa by acting as antioxidants, free-radical scavengers and as regulators of the integrity ARTICLE IN PRESS www.elsevier.com/locate/idairyj 0958-6946/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.idairyj.2005.10.027 Corresponding author. Tel./fax: +55 19 32877400. E-mail address: sgarb@fea.unicamp.br (V.C. Sgarbieri).