Anti-stress effect of milk-derived iron binding proteins

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Lactoferrin(LF) is known as an iron-binding glycoprotein, specially contained in milk. We have shown that intra-duodenally administered bovine-LF(bLF) was absorbed from intestine and transported into blood circulation via receptor mediated system. We found that the bLF was finally transported into cerebrospinal fluid. However, its physiological effects in the central nervous system(CNS) are still unclear.In this project, suppressive effects of bLF on psychological distress were investigated in neonatal and adult rats. Intraperitonealy injected bLF (100 mg/kg) reduced behavioral responses to the stress in maternally separated pups or in a conditioned-fear-induced freezing test and an elevated plus-maze test in adult rats. Interestingly, bLF suppressed psychological distress not only in pups but also in adult rats. This suppressive effect of bLF was reversed by pre-treatment with naloxone, an opioid receptor antagonist, at a dose of 1 mg/kg (ip). N^ω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase(NOS) inhibitor, also blocked the suppressive effect of bLF. Additionally, combined application of a low dose of bLF (30 mg/kg, ip) and L-arginine (30 and 100 mg/kg, ip) potentiatively suppressed behavioral responses to the psychological stress. These results suggest that bLF has suppressive effects on the psychological distress, especially under the condition of moderate stress. Furthermore, bLF possibly enhances an endogenous opioidergic system via nitric oxide synthase activation.