Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury

Teng, Ru-Jeng; Jing, Xin; Michalkiewicz, Teresa; Afolayan, Adeleye J.; Wu, Ting; Konduri, Girija G.

doi:10.1152/ajplung.00405.2016

Cited by 77 publications

(92 citation statements)

References 55 publications

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“…In contrast, bronchopulmonary dysplasia (BPD) is a condition affecting ventilated premature neonates that develops as a result of hyperoxia and also appears to involve ER stress. In animal models of BPD hyperoxia in neonates drives ROS production, ER stress and ER stress‐induced apoptosis in the alveolar epithelium providing an explanation for the alveolar damage characteristic of BPD 108, 109…”

Section: Oxidative and Er Stress In Acute Respiratory Conditionsmentioning

confidence: 99%

Oxidative and endoplasmic reticulum stress in respiratory disease

2018

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Oxidative stress and endoplasmic reticulum (ER) stress are related states that can occur in cells as part of normal physiology but occur frequently in diseases involving inflammation. In this article, we review recent findings relating to the role of oxidative and ER stress in the pathophysiology of acute and chronic nonmalignant diseases of the lung, including infections, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. We also explore the potential of drugs targeting oxidative and ER stress pathways to alleviate disease.

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Section: Oxidative and Er Stress In Acute Respiratory Conditionsmentioning

confidence: 99%

Oxidative and endoplasmic reticulum stress in respiratory disease

2018

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“…However, several studies have tried to address mechanistic or molecular mechanisms of action, especially in animal hyperoxia models. Caffeine is thought to reduce inflam-mation, 26,27 attenuate endoplasmic stress 28 and prevents hyperoxia -induced functional and structural lung damage 26 in animal models. Potentially adverse role of caffeine on alveolar development with increased inflammation, apoptosis and decreased expression of A2a receptors is reported in murine model hyperoxia-induced alveolar hypoplasia.…”

Section: Caffeine and Bronchopulmonary Dysplasiamentioning

confidence: 99%

Caffeine, Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes in Premature Infants

Kumar¹

2018

Pediatr Neonatal Nurs Open J

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Caffeine, a stimulant is the most widely used drug in the world in adults with increasing usage in children. It is commonly used in the treatment of apnea of prematurity in premature infants. Caffeine in a randomized trial has been shown to reduce the incidence of bronchopulmonary dysplasia in infants <1250 grams birth weight when used to treat apnea of prematurity in these infants. In the same cohort of infants, caffeine improved neurodevelopmental outcomes and survival at 18 months of age and was found to be safe without any adverse events up to 11 years of age. Caffeine is an adenosine receptor antagonist and inhibits adenosine receptors at physiologic concentrations with important effects on behavior and cognitive functions. However, higher doses of caffeine may inhibit the enzyme phosphodiesterase and affect vascular smooth muscle function. Anti-oxidant, anti-inflammatory and antiapoptotic properties of caffeine and its ability to scavenge reactive oxygen species may contribute to its lung and neuroprotective effects in premature infants. Animal studies on whether caffeine is protective to the lung are not conclusive at this time. Similarly, caffeine is demonstrated to have adverse effects on brain development in animal studies. Despite the beneficial effects of caffeine in premature infants when administered in the neonatal period, the long-term effects on adult-oriented disease such as cardio-metabolic disease and neurobehavioral states in children and adults needs further study.

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“…These models can be used to study the effect of therapeutic interventions such as caffeine, which are not completely understood [29][30][31]. In addition to antagonism of adenosine receptors [32], anti-inflammatory effects, and the reduction of stress on the endoplasmic reticulum, anti-oxidant properties per se have also been discussed [33][34][35][36]. Therefore, this study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of BPD in the newborn rat.…”

Section: Introductionmentioning

confidence: 99%

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

et al. 2019

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Background: While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats. Methods: Newborn Wistar rats were exposed to 21% or 80% oxygen for 3 (P3) or 5 (P5) postnatal days with or without recovery on room air until postnatal day 15 (P15) and treated with vehicle or caffeine (10 mg/kg) every 48 h beginning on the day of birth. The lung tissue of the rat pups was examined for oxidative stress response at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR. Results: Lungs of newborn rats, corresponding to the saccular stage of lung development and to the human lung developmental stage of preterms, showed increased rates of total glutathione and hydrogen peroxide, oxidative damage to DNA and lipids, and induction of second-phase mediators of antioxidative stress response (superoxide dismutase, heme oxygenase-1, and the Nrf2/Keap1 system) in response to hyperoxia. Caffeine reduced oxidative DNA damage and had a protective interference with the oxidative stress response. Conclusion: In addition to the pharmacological antagonism of adenosine receptors, caffeine appears to be a potent antioxidant and modulates the hyperoxia-induced pulmonary oxidative stress response and thus protective properties in the BPD-associated animal model. Free-radical-induced damage caused by oxidative stress seems to be a biological mechanism progress of newborn diseases. New aspects of antioxidative therapeutic strategies to passivate oxidative stress-related injury should be in focus of further investigations.

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Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury

Cited by 77 publications

References 55 publications

Oxidative and endoplasmic reticulum stress in respiratory disease

Oxidative and endoplasmic reticulum stress in respiratory disease

Caffeine, Bronchopulmonary Dysplasia and Neurodevelopmental Outcomes in Premature Infants

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

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