Background: Our previous study showed that resveratrol attenuates apoptosis and mitochondrial dysfunction in alveolar epithelial cell injury induced by hyperoxia by activating the SIRT1/PGC-1α signaling pathway. In the present study, we investigated whether resveratrol protects against hyperoxia-induced lung injury in neonatal rats by activating SIRT1/PGC-1α signaling pathway. Methods: Naturally delivered neonatal rats were randomly divided into six groups: normoxia + normal saline (NN), normoxia + dimethyl sulfoxide (ND), normoxia + resveratrol (NR), hyperoxia + normal saline (HN), hyperoxia + dimethyl sulfoxide (HD), and hyperoxia + resveratrol (HR). Lung tissue samples were collected on postnatal days (PD) 1, 7 and 14. Hematoxylin and eosin staining was used to evaluate lung development. Dual immunofluorescence staining, real time-polymerase chain reaction and western blotting were used to evaluate the levels of SIRT1, PGC-1α, Nrf1, Nrf2, TFAM and citrate synthase, the number of mitochondrial DNA and mitochondrial, the integrity of mitochondrial DNA, and the expression of TFAM in mitochondria. Results: We found that hyperoxia insulted lung development, whereas resveratrol attenuated the hyperoxia lung injury. Resveratrol significantly upregulated the levels of SIRT1, PGC-1α, Nrf1, Nrf2, TFAM and citrate synthase, promoted TFAM expression in the mitochondria, and increased the copy number of ND1 and the ratio of ND4/ND1. Conclusions: Our data suggest that resveratrol attenuates hyperoxia-induced lung injury in neonatal rats and this was achieved, in part, by activating the SIRT1/PGC-1α signaling pathway to promote mitochondrial biogenesis.

Background Neonatal hyperoxic brain injury is caused by exposure to hyperphysiological oxygen content during the period of incomplete development of the oxidative stress defence system, resulting in a large number of reactive oxygen species (ROS) and causing damage to brain tissue. Mitochondrial biogenesis refers to the synthesis of new mitochondria from existing mitochondria, mostly through the PGC-1α/Nrfs/TFAM signalling pathway. Resveratrol (Res), a silencing information regulator 2-related enzyme 1 (Sirt1) agonist, has been shown to upregulate the level of Sirt1 and the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). We speculate that Res has a protective effect on hyperoxia-induced brain injury through mitochondrial biogenesis. Methods Sprague-Dawley (SD) pups were randomly divided into the nonhyperoxia (NN) group, the nonhyperoxia with dimethyl sulfoxide (ND) group, the nonhyperoxia with Res (NR) group, the hyperoxia (HN) group, the hyperoxia with dimethyl sulfoxide (HD) group, and the hyperoxia with Res (HR) group within 12 h after birth. The HN, HD, and HR groups were placed in a high-oxygen environment (80‒85%), and the other three groups were placed in the standard atmosphere. The NR and HR groups were given 60 mg/kg Res every day, the ND and HD groups were given the same dose of dimethyl sulfoxide (DMSO) every day, and the NN and HN groups were given the same dose of normal saline every day. On postnatal day (PN) 1, PN7, and PN14, brain samples were acquired for HE staining to assess pathology, TUNEL to detect apoptosis, and real-time quantitative polymerase chain reaction and immunoblotting to detect the expression levels of Sirt1, PGC-1α, nuclear respiratory factor 1 (Nrf1), nuclear respiratory factor 2 (Nrf2) and mitochondrial transcription factor A (TFAM) in brain tissue. Results Hyperoxia induced brain tissue injury; increased brain tissue apoptosis; inhibited Sirt1, PGC-1α, Nrf1, Nrf2, TFAM mRNA expression in mitochondria; diminished the ND1 copy number and ND4/ND1 ratio; and decreased Sirt1, PGC-1α, Nrf1, Nrf2, and TFAM protein levels in the brain. In contrast, Res reduced brain injury and attenuated brain tissue apoptosis in neonatal pups and increased the levels of the corresponding indices. Conclusion Res has a protective effect on hyperoxia-induced brain injury in neonatal SD pups by upregulating Sirt1 and stimulating the PGC-1α/Nrfs/TFAM signalling pathway for mitochondrial biogenesis.

With recent advances in neonatal intensive care, preterm infants are surviving into adulthood. Nonetheless,epidemiological data on the health status of these preterm infants has begun to reveal a worrying theme; prematurity and the supplemental oxygen therapy these infants receive after birth appear to be risk factors for kidney disease in in adulthood, affecting their quality-of-life. As the incidence of chronic kidney disease and the survival time of preterm infants both increase, the management of hyperoxia-induced renal disease is becoming increasingly relevant to neonatologists. The mechanism of this increased risk is currently unknown, but prematurity itself and the hyperoxia exposure after birth may predispose to disease by altering the normal trajectory of kidney maturation. This article reviews altered renal reactivity due to hyperoxia, the possible mechanisms of renal injury due to hyperoxia, and the role of resveratrol in renal injury.