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

PLoS One. 2016 Jul 20;11(7):e0159633. doi: 10.1371/journal.pone.0159633. eCollection 2016.


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.

MeSH terms

  • Acute Lung Injury / diet therapy*
  • Acute Lung Injury / physiopathology
  • Animals
  • Animals, Newborn
  • Bronchoalveolar Lavage Fluid
  • Diet
  • Disease Models, Animal
  • Fruit and Vegetable Juices*
  • Hyperoxia / diet therapy*
  • Hyperoxia / physiopathology
  • Inflammation / diet therapy*
  • Inflammation / physiopathology
  • Lung / drug effects
  • Lung / physiopathology
  • Mice
  • Oxidative Stress / drug effects
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / physiopathology
  • Solanum lycopersicum / chemistry*

Grants and funding

This study was supported by the National Health and Medical Research Council of Australia ( Program Grant #606789 and Monash University, Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.