Abstract
Purpose: To determine the efficacy of resveratrol in mitigating necrotizing enterocolitis (NEC) in neonatal rats.Methods: Necrotizing enterocolitis (NEC) was induced in neonatal rats using hypoxia and hypothermia. At the completion of treatment, the intestinal tissues of the rats were isolated for evaluation of various biochemical parameters.Results: There was significant increase in the levels of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and oxidative stress markers (MDA, xanthine oxidase and nitric oxide) in intestinal tissues of NEC rats (p < 0.05). However, resveratrol treatment led to significant decrease in the levels of cytokines and oxidative stress parameters, relative to the NEC group (p < 0.05). Furthermore, Western blotting resultsshowed up-regulation in protein expressions of inflammatory cytokines in NEC rats. However, the protein expressions of inflammatory cytokines were down-regulated in the NEC rats on treatment with resveratrol. Moreover, resveratrol reversed the NEC-induced up-regulations of Bax and caspase-3, as well as NEC-mediated down-regulation of Bcl-2.Conclusion: These results demonstrate that resveratrol mitigates NEC-induced intestinal damage in neonatal rats via anti-inflammatory, anti-apoptotic and antioxidant mechanisms of action. Therefore, resveratrol is a potential therapeutic agent for NEC.
Highlights
Necrotizing enterocolitis (NEC) is a serious inflammatory disease of the gastrointestinal system, and it is associated with significant morbidity and mortality
Treatment of the NEC pups with resveratrol led to significant decreases in levels of TNF-α, IL-6 and IL-1β, The levels of oxidative stress markers i.e., malondialdehyde (MDA) and xanthine oxidase (XO) were significantly increased in the intestinal homogenate of NEC neonatal rats (p < 0.05; Figure 1)
Treatment with resveratrol significantly reduced the oxidative stress by reducing the levels of MDA and XO (p < 0.05)
Summary
Necrotizing enterocolitis (NEC) is a serious inflammatory disease of the gastrointestinal system, and it is associated with significant morbidity and mortality. Studies have shown that the interaction between ROS generated as result of I/R injury to premature gut, and decreased antioxidant status, may lead to the development of NEC [4] Pathological factors such as immature antioxidant defences and increased ROS predispose to intestinal oxidative damage in premature newborns. NEC was induced using the hypoxia and hypothermia procedure as previously described by Karadag et al The neonatal rats were made hypoxic by exposing them to 100 % nitrogen gas for 2 min, followed by instant exposure to cold stress at 4 °C for 10 min. The rats were randomly assigned to four groups: control, NEC, resveratrol-alone and Nitrite levels. Effect of resveratrol on intestinal levels of MDA and xanthine oxidase in NEC neonatal rats.
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