Iyose, Tokyo 204-8588, Japan Division of Hygienic Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan; E-Mails: [email protected] (M.I.); [email protected] (K.I.) Meals ATM Inhibitor Source Science Technologies Institute, Morinaga Milk Business Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 252-8583, Japan; E-Mails: [email protected] (H.O.); [email protected] (H.W.) Author to whom correspondence really should be addressed; E-Mail: [email protected]; Tel./Fax: +81-424-95-8652. Received: 19 November 2013; in revised form: 24 December 2013 / Accepted: 9 January 2014 / Published: 14 JanuaryAbstract: In this study, we examined the protective impact of lactoferrin against DNA damage induced by several hydroxyl radical generation systems. Lactoferrin (LF) was examined with regard to its possible function as a scavenger against radical oxygen species using bovine milk LF. Native LF, iron-saturated LF (holo-LF), and apolactoferrin (apo-LF) proficiently suppressed strand breaks in plasmid DNA resulting from hydroxyl radicals made by the Fenton reaction. Also, each native LF and holo-LF clearly protected calf thymus DNA from fragmentation as a result of ultraviolet irradiation inside the presence of H2O2. We also demonstrated a protective effect of all three LF molecules against 8-hydroxydeoxyguanosine (8-OHdG) formation in calf thymus DNA following ultraviolet (UV) irradiation with H2O2. Our outcomes clearly indicate that native LF has reactive oxygen species-scavenging capacity, independent of its nature as a masking element for transient metals. We also demonstrated that the protective impact of LF against oxidative DNA damage is because of degradation of LF itself, that is additional susceptible to degradation than other bovine milk proteins.Int. J. Mol. Sci. 2014, 15 Keywords and phrases: lactoferrin; bovine milk; DNA damage; hydroxyl radical; UV irradiationAbbreviations: LF, lactoferrin; EDTA, ethylenediaminetetraacetic acid; ROS, reactive oxygen species; 8-OHdG, 8-hydroxydeoxyguanosine; iron-saturated lactoferrin, holo-LF; apolactoferrin, apo-LF; MLF, native milk lactoferrin. 1. Introduction Lactoferrin (LF) is an 80-kDa non-heme iron-binding glycoprotein that belongs for the transferrin family . In mammals, it truly is discovered at most mucosal websites and inside the secondary granules of neutrophils . Lactoferrin plays a key role in a Bcl-2 Inhibitor manufacturer number with the host’s 1st line defense mechanisms and contributes to a range of physiological responses at both the cellular and organ level [4,5]. Lactoferrin plays a crucial function in immune homeostasis and functions to cut down oxidative stress at the molecular level, as a result, controlling excessive inflammatory responses . Oxidative tension happens when the production of potentially destructive reactive oxygen species (ROS) exceeds the body’s personal natural antioxidant defense mechanisms, which benefits in cellular harm. A cell is able to overcome and repair compact perturbations; having said that, severe oxidative anxiety can cause cell death. While moderate levels of oxidative strain can trigger apoptosis, far more intense stress can bring about tissue necrosis . Transitional metals could possibly be mediator in the cellular response to oxidative pressure. In particular, trace iron can have detrimental effects inside the setting of oxidative injury. Iron crucially modulates the production of ROS by catalyzing a two-step course of action referred to as the Haber-Weiss reaction . Beneath normal physiological situations, the production and neutralizati.