Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus)

Abstract

Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ) could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J) breathed either 65% O2 (hyperoxia) or room air from birth until postnatal day 7 (P7d); some underwent necropsy at P7d and others were raised in room air until adulthood (P56d). In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water) from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC), markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression), inflammation (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression), collagen (COL) and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d) and leukocytes in BALF (at P56d). At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects of TJ are likely due to elevation of circulating antioxidant concentrations.

Status of Retinoids and Carotenoids and Associations with Clinical Outcomes in Maternal-Infant Pairs in Nigeria

“…Biologically significant carotenoids include α-carotene, β-carotene, and β-cryptoxanthin, which have pro-vitamin A activity. Lycopene and lutein, while not possessing pro-vitamin A activity, are effective anti-oxidants [ 12 , 13 , 14 ]. Carotenoids are found primarily in foods of plant origin, including leafy green and red, yellow, and orange fruits and vegetables [ 12 , 15 ].…”

Modelling bronchopulmonary dysplasia in mice: how much oxygen is enough?

“…However, there is a pronounced lack of standardisation of BPD mouse models, with over 41 different oxygen-exposure protocols reported in a 30-month period alone ( Silva et al, 2015 ). Although initially very high (90-100%) oxygen concentrations were employed in the past as an injurious stimulus in BPD models, and indeed, still are by many groups; there has been a gradual shift in the degree of oxygen toxicity employed, with increased instances of oxygen concentrations below 80% O 2 becoming increasingly evident in recent published studies ( Bouch et al, 2016 , 2015 ; Ehrhardt et al, 2016 ; Maduekwe et al, 2015 ; Reyburn et al, 2016 ; Sozo et al, 2015 ; Wang et al, 2014 ; Yee et al, 2016 ). In some instances, the lack of model standardisation might have resulted in opposite findings when evaluating the same candidate therapeutic intervention ( Silva et al, 2015 ).…”

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads

“…The effects of supplementing individual compounds, such as lycopene, merit much consideration prior to implementation. Clinical trials with other single small molecules, like vitamin E, vitamin C, or β-carotene have largely been disappointing [ 40 ], and likewise, laboratory experiments using single antioxidants have shown them to be largely ineffective in ameliorating hyperoxia-induced injury [ 3 , 41 ]. An imbalance between different antioxidants can potentially result in tissue damage [ 3 , 42 ].…”

“…Clinical trials with other single small molecules, like vitamin E, vitamin C, or β-carotene have largely been disappointing [ 40 ], and likewise, laboratory experiments using single antioxidants have shown them to be largely ineffective in ameliorating hyperoxia-induced injury [ 3 , 41 ]. An imbalance between different antioxidants can potentially result in tissue damage [ 3 , 42 ]. Antioxidant defense systems are multifaceted, thus supplementation with a single molecule, unless a deficiency is present, is likely to have little effect on the development of a disease or adverse outcome.…”

“…Oxidative stress results from an imbalance between the production of potentially harmful reactive oxygen species (ROS) and antioxidants and their repair processes [ 1 , 2 , 3 , 4 ]. During pregnancy, an increase in oxidative stress can raise the risk of many adverse outcomes, including gestational diabetes, preeclampsia, pregnancy-induced hypertension, and intrauterine growth restriction [ 1 , 2 , 5 , 6 , 7 , 8 ].…”