Human milk has anti-oxidant properties to protect premature infants

Human milk (HM) is recognized as the optimal form of nutrition in the newbom period, providing nutrients and a variety of components (minerals, vitamins, enzymes, hormones, growth factors, and immunoglobulins) that are very important for growth and healthy development. In the case of premature (PM) infants, functional and in certain cases, structural development of most organ systems is completed in the weeks following birth. PM infants do not get enough oxygen and may require supplemental oxygen as high as 95%. This high level of inspired oxygen necessary to maintain arterial oxygen tension exposes these infants to more reactive oxygen species (ROS) compared with full term infants. ROS may lead to diseases associated with prematurity, including necrotizing enterocolitis, retinopathy of prematurity, intraventricular-periventricular hemorrhage, and bronchopulmonary dysplasia. There is then a need to reduce oxidative stress or boost antioxidant defenses in these vulnerable infants. Data suggest that HM has unique antioxidant properties that will assist the premature infant in coping with the increased oxidative stress. HM antioxidant components include the enzymes superoxide dismutase for dismutation of superoxide anion, catalase for degradation of hydrogen peroxide (H2O2), glutathione peroxidase for destruction of H2O2 and organic peroxides. Human milk contains other molecules including cysteine, vitamins C and E, which are scavengers of oxygen radicals

UV resonance Raman spectroscopy probes the amide II′p band position in short breast milk peptides with antioxidant activity

UV resonance Raman spectroscopic study of six short proline-containing peptides with antioxidant activity isolated from human breast milk was performed. The amide II′ proline spectroscopic band was used to estimate relative cis trans isomerization state of proline amide bonds in the different peptides. Antioxidant activity of the peptides was determined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay and linoleic acid emulsion assay. Although no clear correlation between the amide II′p position and antioxidant activity of the peptides was observed, they both were found to be sensitive to the presence and/or relative position of proline and tyrosine residues in the peptide. Copyrigh

Evaluation of antioxidant capacity and aroma quality of breast milk

Objective: It is important to understand the difference and similarity in antioxidant capacity and aroma quality between formula and breast milk for purposes of modifying infant formulas. We evaluated the antioxidant properties and aroma quality of infant formula and breast milk. Methods: Six breast milk samples and four infant formulas were used. Antioxidant properties were measured using the following methods: 2,2-diphenyl-1-picryhydrazyl free radical scavenging capacity, oxygen radical absorbance capacity, total phenolic content, and phenolic composition. Aroma quality was determine

Tryptophan from human milk induces oxidative stress and upregulates the Nrf-2-mediated stress response in human intestinal cell lines

Chemical screening of digested human milk protein using the oxygen radical absorbance capacity (ORAC FL) antioxidant assay confirmed the presence of a peptide fraction (PF23) with high antioxidant activity [5.53 mmol Trolox equivalents (TE)/g] that contained tryptophan as a main component. We evaluated the effects of both PF23 and tryptophan alone on the modulation of oxidative stress in cultured intestinal cells using a dichlorofluorescein diacetate probe. Despite the high ORAC FL value, PF23 enhanced (P< 0.05) 2, 2'-azobis (2-amidinopropane) dihydrochloride (peroxyl radical generator)-induced intracellular oxidation in the Caco-2 human adenocarcinoma cell line, suggesting prooxidant activity. Compared to selected peptide fractions with relatively lower ORAC FL values, PF23 induced oxidative stress more than all other peptide fractions tested (P< 0.05) and contained more tryptophan than the others (P< 0.05). Similar prooxidant activity was observed for tryptophan when it was added to culture medium for both the Caco-2 cells and FHs 74 Int primary fetal enterocytes, while also exhibiting a high ORAC FL value (9.69 mmol TE/g). The effect of tryptophan that involves activation of the Nrf-2 pathway and transcription of antioxidant enzymes was therefore investigated in FHs 74 Int cells. Exposure of infant intestinal cells to tryptophan resulted in Nrf-2 activation and an increase in the gene transcript level of glutathione peroxidase 2. We conclude that tryptophan-induced oxidative stress associated with tryptophan-containing milk peptides induces an adaptive response that involves the activation of the antioxidant responsive signaling pathway in intestinal cells

Tryptophan released from mother's milk has antioxidant properties

Bioactive factors in human milk (HM) are crucial to the health of newborns, especially preterm infants. These compounds assist in reducing the oxidative stress that may occur as a result of combined exposure to supplemental oxygen and immature physiologic defenses. To identify the components in HM that contribute to its greater resistance to oxidative stress compared with infant formulae, enzymatic hydrolysates of HM were prepared, ultrafiltered, separated, and analyzed for antioxidant potential. The antioxidant activity [μM Trolox equivalent (TE/g)] of nondigested milk, whole digested milk, and derived ultrafiltrates were 80.4 ± 13.3, 159.0 ± 5.6, and 127.4 ± 3.1, respectively. An HPLC fraction denoted as fraction 23 (5274 ± 630 μM TE/g) was obtained and its constituents identified as tryptophan (Trp), peptides HNPI, and PLAPQA. Scavenging activity was not observed for PLAPQA, whereas moderate activity was associated with HNPI (144 ± 10.7 μM TE/g) and very high activity to Trp (7986 ± 468 μM TE/g). Trp addition to HM and two infant formulas significantly increased formulae antioxidant properties. Trp appeared to be a powerful free radical scavenger naturally present in HM. Its antioxidant effects and potential application in the diets of infants, particularly preterm, must be examined further

Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors

Endometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer cell viability in response to chemotherapy in vitro and in vivo. A lentiviral-based shRNA knockdown approach was used to generate stable PGRMC1-intact and PGRMC1-deplete Ishikawa endometrial cancer cell lines that also lacked expression of the classical progesterone receptor (PGR). Progesterone treatment inhibited mitosis of PGRMC1-intact, but not PGRMC1-deplete cells, suggesting that PGRMC1 mediates the anti-mitotic actions of P4. To test the hypothesis that PGRMC1 attenuates chemotherapy-induced apoptosis, PGRMC1-intact and PGRMC1-deplete cells were treated in vitro with vehicle, P4 (1 μM), doxorubicin (Dox, 2 μg/ml), or P4 + Dox for 48 h. Doxorubicin treatment of PGRMC1-intact cells resulted in a significant increase in cell death; however, co-treatment with P4 significantly attenuated Dox-induced cell death. This response to P4 was lost in PGRMC1-deplete cells. To extend these observations in vivo, a xenograft model was employed where PGRMC1-intact and PGRMC1-deplete endometrial tumors were generated following subcutaneous and intraperitoneal inoculation of immunocompromised NOD/SCID and nude mice, respectively. Tumors derived from PGRMC1-deplete cells grew slower than tumors from PGRMC1-intact cells. Mice harboring endometrial tumors were then given three treatments of vehicle (1:1 cremophor EL: ethanol + 0.9% saline) or chemotherapy [Paclitaxel (15 mg/kg, i.p.) followed after an interval of 30 minutes by CARBOplatin (50 mg/kg)] at five day intervals. In response to chemotherapy, tumor volume decreased approximately four-fold more in PGRMC1-deplete tumors when compared with PGRMC1-intact control tumors, suggesting that PGRMC1 promotes tumor cell viability during chemotherapeutic stress. In sum, these in vitro and in vivo findings demonstrate that PGRMC1 plays a prominent role in the growth and chemoresistance of human endometrial tumors