Lycopene supplementation reduces inflammatory, histopathological and DNA damage in an acute lung injury rabbit modelObjective To investigate the effects of lycopene supplementation on inflammation, lung histopathology and systemic DNA damage in an experimentally induced lung injury model, ventilated by conventional mechanical ventilation and high-frequency oscillatory ventilation, compared with a control group.
Methods Fifty-five rabbits sampled by convenience were supplemented with 10mg/kg lycopene for 21 days prior to the experiment. Lung injury was induced by tracheal infusion of warm saline. The rabbits were randomly assigned to the control group and subjected to protective conventional mechanical ventilation (n = 5) without supplementation or the experimental group that was subjected to acute lung injury and provided conventional mechanical ventilation and high-frequency oscillatory ventilation with and without lycopene supplementation (n = 10 rabbits in each group). Lung oxidative stress and the inflammatory response were assessed based on the number of polymorphonuclear leukocytes in bronchoalveolar lavage fluid, DNA damage and pulmonary histological damage.
Results A significant worsening of oxygenation and a decrease in static lung compliance was noted in all groups after pulmonary injury induction (partial pressure of oxygen before 451.86 ± 68.54 and after 71 ± 19.27, p < 0.05). After 4 hours, the high-frequency oscillatory ventilation groups with and without lycopene supplementation as well as the group receiving protective conventional mechanical ventilation with lycopene supplementation showed significant oxygenation improvement compared with the protective conventional mechanical ventilation group without supplementation (partial pressure of oxygen of the group with mechanical ventilation without lycopene of 102 ± 42, of the group that received conventional protective mechanical ventilation with lycopene supplementation of 362 ± 38, of the high-frequency group without lycopene supplementation of 420 ± 28 and of the high-frequency group with lycopene supplementation of 422 ± 25; p < 0.05). Compared with rabbits not receiving supplementation, those in the groups that received protective conventional mechanical ventilation with lycopene supplementation and high-frequency oscillatory ventilation with lycopene supplementation had significantly less inflammation as well as less histological injury (p < 0.05). Compared with rabbits subjected to protective conventional mechanical ventilation, significantly lower DNA damage was observed in rabbits supplemented with lycopene (p < 0.05).
Conclusion Lycopene supplementation reduces inflammatory and histopathological lung injuries, regardless of the associated ventilatory mode. In addition, lycopene improved oxygenation and reduced DNA damage when protective conventional mechanical ventilation was used.
Respiratory distress syndrome; Lung injury; Respiration, artificial; Carotenoids; DNA damage; Inflammation
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T - time; CMV - mechanical ventilation group without lycopene; CMVL - mechanical ventilation with lycopene; HFL - high frequency with lycopene; HF - high frequency without lycopene; CG - control group; PEEP - positive end-expiratory pressure.
Statistical tests: Repeated-measures ANOVA in independent groups complemented with the Bonferroni multiple comparisons test. * p < 0.05 at T0, comparing the control group with the other groups; # p < 0.05 at T240, comparing the control group, high-frequency with lycopene, high-frequency without lycopene, and mechanical ventilation with lycopene groups with the mechanical ventilation group without lycopene. CG - control group; CMV - mechanical ventilation group without lycopene; HF - high-frequency group without lycopene; CMVL - mechanical ventilation with lycopene; HFL - high-frequency with lycopene.
There was no difference between mechanical ventilation group without lycopene (76.5 ± 17.5) and high-frequency oscillatory ventilation (22 ± 38) or between conventional mechanical ventilation group (2 ± 1.5) and high-frequency (5.5 ± 7.5), p > 0.05. However, the groups supplemented with lycopene presented a lower number of polymorphonuclear leukocytes, ‘a’ versus ‘b’, p < 0,05. CMV - conventional mechanical ventilation group without supplementation; HF - high-frequency oscillatory ventilation group without supplementation; CMVL - conventional mechanical ventilation group supplemented with lycopene; HFL - high-frequency oscillatory ventilation group supplemented with lycopene. Statistical test: Kruskal–Wallis analysis of variance complemented by Dunn’s multiple comparisons test.
CG - control group; CMV - conventional mechanical ventilation group without supplementation; HF - high-frequency oscillatory ventilation group without supplementation; CMVL - conventional mechanical ventilation group supplemented with lycopene; HFL - high-frequency oscillatory ventilation group supplemented with lycopene. Statistical test: Kruskal–Wallis nonparametric ANOVA complemented with Dunn’s multiple comparisons test. The data are expressed in boxplots, and their median values are shown. Compared with conventional mechanical ventilation group and high-frequency without supplementation, control group, high-frequency oscillatory ventilation group supplemented with lycopene and conventional mechanical ventilation group supplemented with lycopene presented significantly lower values (p < 0.05).
CG - control group; CMV - conventional mechanical ventilation group without supplementation; CMVL - conventional mechanical ventilation group supplemented with lycopene; HF - high-frequency oscillatory ventilation group without supplementation; HFL - high-frequency oscillatory ventilation group supplemented with lycopene. Data are shown as the median (range). Kruskal–Wallis analysis of variance was used, with subsequent comparisons by the Dunn test.
CG - control group; CMV - conventional mechanical ventilation group without supplementation; HF - high-frequency oscillatory ventilation group without supplementation; CMVL - conventional mechanical ventilation group supplemented with lycopene; HFL - high-frequency oscillatory ventilation group supplemented with lycopene. Statistical test: analysis of variance complemented with Tukey’s multiple comparisons test. The data are expressed as the means ± standard deviations. *p < 0.05 between conventional mechanical ventilation group without supplementation and conventional mechanical ventilation group supplemented with lycopene.