Road traffic noise exposure and its impact on health: evidence from animal and human studies—chronic stress, inflammation, and oxidative stress as key components of the complex downstream pathway underlying noise‑induced non‑auditory health effects

Vol:.(1234567890) Environmental Science and Pollution Research (2024) 31:46820–46839 https://doi.org/10.1007/s11356-024-33973-9 REVIEW ARTICLE Road traffic noise exposure andits impact onhealth: evidence fromanimal andhuman studies—chronic stress, inflammation, andoxidative stress askey components ofthecomplex downstream pathway underlying noise‑induced non‑auditory health effects AneArregi1,2· OscarVegas1,2· AitanaLertxundi2,3,4· AnaSilva5,6· IsabelFerreira5,6· AinhoaBereziartua2· MariaTeresaCruz5,6,7· NereaLertxundi1,2,3 Received: 26 October 2023 / Accepted: 8 June 2024 / Published online: 8 July 2024 © The Author(s) 2024 Abstract In heavily urbanized world saturated with environmental pollutants, road traffic noise stands out as a significant factor contributing to widespread public health issues. It contributes in the development of a diverse range of non-communicable diseases, such as cardiovascular diseases, metabolic dysregulation, cognitive impairment, and neurodegenerative disorders. Although the exact mechanisms behind these non-auditory health effects remain unclear, the noise reaction model centres on the stress response to noise. When exposed to noise, the body activates the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system, leading to the secretion of stress hormones like catecholamines and cortisol. Prolonged exposure to noise-induced stress results in chronic inflammation and oxidative stress. This review underscores the role of inflammation and oxidative stress in the progression of noise-induced vascular dysfunction, disruption of the circadian rhythm, accelerated aging, neuroinflammation, and changes in microbiome. Additionally, our focus is on understanding the interconnected nature of these health outcomes: These interconnected factors create a cascade effect, contributing to the accumulation of multiple risk factors that ultimately lead to severe adverse health effects. Keywords Road traffic noise· Environmental stressor· Inflammation· Oxidative stress· Non-auditory health effects Abbreviations ACTH Adrenocorticotropic hormone AD Alzheimer’s disease AMPK AMP-activated kinase ADHD Attention-deficit/hyperactivity disorder BMAL1 and BMAL2 Brain and muscle arnt-like protein-1 and protein-2 CVD Cardiovascular disease CLOCK Circadian locomotor output cycles protein kaput CRH Corticotrophin-releasing hormone CRY1 and CRY2 Cryptochromes 1 and 2 Responsible Editor: Philippe Garrigues * Maria Teresa Cruz [email protected] 1 Faculty ofPsychology, University oftheBasque Country (UPV/EHU), 20008SanSebastian, Spain 2 Environmental Epidemiology andChild Development Group, Biogipuzkoa Health Research Institute, Paseo Doctor Begiristain S/N, 20014SanSebastian, Spain 3 Spanish Consortium forResearch On Epidemiology andPublic Health (CIBERESP), Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029Madrid, Spain 4 Department ofPreventive Medicine andPublic Health, Faculty ofMedicine, University oftheBasque Country (UPV/EHU), 48940Leioa, Spain 5 Center forNeuroscience andCell Biology andInstitute forBiomedical Imaging andLife Sciences, University ofCoimbra, 3000-548Coimbra, Portugal 6 Center forInnovative Biomedicine andBiotechnology (CIBB), University ofCoimbra, Coimbra, Portugal 7 Faculty ofPharmacy, University ofCoimbra, 3000-548Coimbra, Portugal 46821Environmental Science and Pollution Research (2024) 31:46820–46839 eNOS Endothelial nitric oxide synthase HO-1 Heme oxygenase-1 HPA Hypothalamic-pituitary-adrenal IHD Ischemic heart disease MACE Major adverse cardiovascular events MAPK Mitogen-activated protein kinases NIH National Institutes Health nNOS Neuronal nitric oxide synthase NO Nitric oxide NF-κB Nuclear factor-κB NRF2 Nuclear factor erythroid 2-related factor 2 OR Odds ratio PER1, PER2, and PER3 Periods 1, 2, and 3 ROS Reactive oxygen species REDD1 Regulated in development and DNA damage responses 1 RR Relative risk SCI Systemic chronic inflammation NOX-2 NADPH oxidase WHO World Health Organization Introduction Currently, 55% of the global population lives in cities and this number projected to rise to 68% by 2050. Europe, in particular, has a higher urban population, with 74% of Europeans currently living in urban areas (United Nations 2018). In this scenario, the establishment of sustainable and healthy urban environments is crucial. Within the exposome, which includes the sum of all environmental contributions during the life course, involving external factors, behavioural factors, lifestyle factors, and biological responses (Daiber etal. 2019), environmental noise stands as the second most serious environmental risk factor in Europe, with air pollution being the primary contributor (European Environment Agency 2020). The World Health Organization (WHO) defines it as noise created from all sources, except workplace noise (WHO 2018). However, according to the Environmental Noise Directive, environmental noise is described as unwanted or harmful sound derived from human activities, including noise emitted by means of transport — road traffic, rail traffic, air traffic, and from sites of industrial activity (Directive 2002/49/EC 2002). This directive defines dayevening-night noise levels above 55dB(A) as harmful, with road traffic noise as the predominant source. More than 113 million people are affected by road traffic noise exposure above the recommended values, meaning that at least 20% of Europeans are exposed to traffic noise levels that can cause adverse health effects. The overall number of people exposed to noise levels above 55dB originated by other means is 22 million for railway noise, 4 million for aircraft noise, and less than 1 million for noise created by industrial activities (WHO 2018). According to several reviews conducted by some WHO expert chairs, exposure to road traffic noise could cause nonauditory health effects, including adverse birth outcomes (Nieuwenhuijsen etal. 2017), cardiovascular disease (CVD) and metabolic effects (van Kempen etal. 2018), sleep disturbances (Basner and McGuire 2018), or cognitive impairment (Clark and Paunovic 2018a). However, the evidence regarding the relationship between environmental noise and some of the mentioned outcomes is very scarce. This does not mean that there is no relationship, but more quality research is needed. Moreover, in Europe, long-term exposure to noise causes 12,000 premature deaths and 48,000 cases of ischemic heart disease per year. Furthermore, 6.5 million people experience chronic sleep disturbances, and 12,500 schoolchildren struggle with learning difficulties (European Environment Agency 2020). In this review, we summarize the current understanding of the molecular pathways and mechanisms underlying the non-auditory health effects of noise. Our objective is to understand how noise cotributes in the most common health outcomes, including inflammation and oxidative stress, vascular dysfunction, dysregulation of the circadian rhythm, metabolic disturbances, age-related diseases, changes in the microbiome, and mental health outcomes. Most reviews addressing the mechanisms underlying noise-induced nonauditory effects have focused on only one health outcome, the most common being vascular dysfunction. However, given the interrelation between these outcomes, this review reinforces the importance of a holistic approach, considering all outcomes and their interactions. Noise reaction model According to the noise reaction model proposed by Babisch (Babisch 2003), noise can induce harmful effects through two pathways. The model suggests that high noise levels (> 85 dBA), can directly cause health problems such as hearing loss or direct physiological changes due to sleep disturbances. In contrast, indirect pathway is related to lower noise levels impairing daily activities, communication or sleep. This pathway involves cognitive perception, leading to cortical activation and emotional responses like annoyance (Münzel etal. 2021). It is believed that when annoyance is high and chronic, a mechanism of psychological habituation occurs: isolation of noise from consciousness and reduction 46822 Environmental Science and Pollution Research (2024) 31:46820–46839 of emotional overload in the prefrontal cortex, resulting in less annoyance (Recio etal. 2016). However, the physiological response to noise persists: It causes a primary stress reaction. Specifically, it triggers the activation of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system. Hence, a cascade of reactions occurs, including the release of stress hormones such as cortisol, adrenaline, and noradrenaline(Daiber etal. 2019). HPA axis activity is governed by three hormones: corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol, the main glucocorticoid in humans. Activation of the HPA axis triggers the release of CRH, which stimulates ACTH production and modulates cortisol synthesis. Elevated cortisol levels serve as a negative feedback mechanism, suppressing the release of CRH and ACTH and thus restoring basal levels of stress hormones (Herman etal. 2016). However, in cases of chronic stress, dysfunction in the HPA axis occurs, and buffering mechanisms may prove insufficient to return to baseline conditions. This physiological phenomenon is known as allostatic load and has been associated with several detrimental health outcomes (Mc Ewen 1998; Guidi etal. 2021). Noise has been identified as a chronic stressor that triggers a chain reaction of oxidative, inflammatory, and metabolic effects, resulting in non-auditory health outcomes (Hahad etal. 2021). A study that associates nighttime aircraft noise exposure with an increased risk of Takotsubo syndrome, a cardiomyopathy linked to excessive stress hormone release, supports this idea of the importance of the indirect pathway (Münzel etal. 2016). Cortisol measurement provides an estimation of HPA axis activity. Acute cortisol levels can be measured in biological samples, namely blood, saliva, and urine samples (Hellhammer etal. 2009; Wright etal. 2015; Mlili etal. 2021). Most of the research has focused on the effect of aircraft noise in salivary cortisol, reporting elevated salivary cortisol levels in participants living near airports (Selander etal. 2009; Lefèvre etal. 2017; Baudin etal. 2019). In contrast, studies in regard of road traffic noise are inconclusive. A systematic review concluded that road traffic noise was related to higher urinary or salivary cortisol levels (Hohmann etal. 2013); however, recent studies have shown no association between road traffic noise and salivary cortisol (Wallas etal. 2018; Bloemsma etal. 2021). Concerning chronic cortisol levels, hair cortisol was reported as a viable tool for assessing the link between environmental noise exposure and chronic stress (Michaud etal. 2022). To the best of our knowledge, only one study measured hair cortisol and found no association between residential exposure to road traffic noise and hair cortisol concentration in 14–15-year-old adolescents (Verheyen etal. 2021). Therefore, it is thought that chronic release of stress hormones due to noise-induced activation of the HPA axis and sympathetic nervous system produces a state of chronic inflammation and oxidative stress, as detailed in Fig.1 Inflammation andoxidative stress Inflammation is the body’s reaction through which immune and non-immune cells are activated, to eradicate harmful stimuli and promote tissue repair and recovery. An important aspect of the inflammatory response is temporal regulation: It is activated when a threat is present and ends once the threat is over (Furman etal. 2019). Factors that induce inflammation (e.g., pathogens, damaged cells, toxic chemicals, and physical and psychological stresses) trigger the production of inflammatory mediators. These mediators activate the downstream components of the inflammatory pathway (Medzhitov 2008; Hahad etal. 2019). This process is regulated and usually lasts for a few days, allowing elimination of the the threat without causing undue tissue damage (Leiba etal. 2023). Any failure in this control could provoke chronic inflammation, characterized by the infiltration of mononuclear immune cells (monocytes, macrophages, lymphocytes, and plasma cells), tissue destruction, and fibrosis (Khansari etal. 2009). While acute inflammation is vital for immune response, systemic chronic inflammation (SCI) has been linked to various diseases such as CVD, cancer, metabolic dysregulation, and neurodegenerative diseases (Furman etal. 2019). The harmful effects of chronic inflammation are mainly caused by overproduction of reactive oxygen species (ROS) and depletion of antioxidants (Halliwell 2006). ROS, unstable molecular species with one or more unpaired electrons, are crucial for the regulation of several signalling pathways (e.g. cell differentiation, proliferation and antioxidant regulation) (Halliwell and Gutteridge 1985). Nonetheless, an imbalance between the production of ROS and antioxidant defenses, known as oxidative stress, can lead to a toxic increase in ROS levels, which can induce cell damage. Elevated ROS levels can generate other ROS, such as hydrogen peroxide (H2O2), superoxide anions (O2•−), and hydroxyl radicals (OH•). This, in turn, results in oxidative damage to cellular lipids and proteins and mutations in the genome, ultimately leading to cell death (Halliwell and Gutteridge 1985; Hajam etal. 2022). ROS-induced oxidative stress disrupts various organ systems, including the nervous system, kidneys, liver, and cardiovascular system (Khansari etal. 2009). Several molecular pathways are activated in response to stress, leading to the excessive generation of ROS and inflammatory signalling. Myeloid cells trigger the initial response in the inflammatory process. Once recruited to the injury site, these cells generate ROS, as well as inflammatory cytokines, chemokines, and prostaglandins. 46823Environmental Science and Pollution Research (2024) 31:46820–46839 Nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPK) and JAK-STAT signalling pathways (Chen etal. 2018), and the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) inhibit cell death by promoting anti-inflammatory and antioxidant processes. NRF2 appears to serve as a vital protective mechanism against various environmental stressors (Bayo Jimenez etal. 2022). Noise-induced oxidative stress appears to activate NRF2 and trigger the production of its target genes. Conversely, NRF2 deficiency exacerbates noise-induced damage, while its activation has protective effects (Bayo-Jimenez etal. 2021). Fig. 1 Summary of the current knowledge of the mechanism by which road traffic noise induces chronic stress hormones, systemic inflammation, and oxidative stress impact on several health outcomes. As proposed by the noise reaction model, in the indirect pathway, noise causes sleep disturbances and annoyance (represented in the upper side in blue), which cause HPA axis and SNS activation: higher levels of cortisol, systemic inflammation, and oxidative stress (in gray) cause the main detrimental health outcomes induced by reactive oxygen species (ROS) (summarized in yellow). Changes in the microbiome, noise-induced vascular dysfunction, neuroinflammation, dysregulation of the circadian rhythm, accelerated aging, and Alzheimer’s disease (AD) like brain, as well as the interrelationships among all of these health outcomes, result in the accumulation of multiple risk factors leading to serious adverse health effects (below in green). Figure made by author, based on the previous research 46824 Environmental Science and Pollution Research (2024) 31:46820–46839 Inflammation andoxidative stress byroad traffic noise exposure Previous studies suggest that inflammation and oxidative stress play key roles in the development of by road traffic noise-induced damage (Daiber etal. 2020). The mechanisms through which it contributes to the overall disease burden remain unclear, primarily due to the absence of well-established research models in both humans and animals. Previous reviews have focused on the role of ROS and inflammation in noise-induced cardiovascular dysfunction (Daiber etal. 2019, 2020; Münzel etal. 2022), dysregulation of the circadian clock (Daiber etal. 2022), neurodegenerative disorders (Manukyan 2022), accelerated aging (Hahad etal. 2021), and psychiatric disorders (Hahad etal. 2022). However, we aim to provide a general overview of this issue and explore the interconnection between the diverse non-auditory health outcomes. Animal studies Experimental research conducted on animal models has shown that noise exposure can lead to extraauditory effects, mostly in the brain and immune system, by triggering oxidative stress (Cheng etal. 2011; Cui and Li 2013; Molina etal. 2016; Pascuan etal. 2014). Manikandan etal. (2006) reported heightened activity of antioxidant enzymes in the hippocampus of rats exposed to acute noise, whereas the activity decreased in those chronically exposed. In another study, mice exhibited increased immune function after 3-day noise exposure, but decreased immune function and oxidative stress were observed in mice exposed for 28days (Zheng and Ariizumi 2007). Münzel etal. established a protocol for aircraft noise exposure to study its effects on mice. They exposed mice to high levels of noise (maximum 85dB, mean 72dB) for 43s, and repeated this exposure 69 times, trying to mimic aircraft noise exposure. This has been fully explained elsewhere (Münzel and Daiber 2018). Following this protocol for four consecutive days, they observed elevated systolic blood pressure, as well as increased levels of catecholamines, angiotensin-II, and endothelin-1. Noise-exposed animals exhibited signs of oxidative stress and inflammation, including eNOS uncoupling as well as increased levels of IL-6, expression of the NADPH oxidase 2 (NOX-2) protein, and nitrotyrosine-positive proteins. Additionally, they observed an increase in the infiltration of natural killer cells and neutrophils into the vasculature (Münzel etal. 2017). Neuroinflammation, cerebral oxidative stress, or circadian dysregulation due to aircraft noise exposure were avoided in Nox2 knockout mice (Kröller-Schön etal. 2018), as well as the pro-inflammatory phenotype and activation of circulating leukocytes (Eckrich etal. 2021). Notably, same noise exposure protocol was used in the aforementioned studies. Frenis etal. found that elimination of monocytes and macrophages (the main lysozyme M-positive inflammatory cells) blocked noise-induced inflammation, oxidative stress, and vascular dysfunction, suggesting the relevance of NOX-2 to noise effects (Frenis etal. 2021a). Given the cross-activation of endothelin-1 and NOX-2, and the fact that both increase under noise exposure, the stimulation of one of them may lead to a vicious cycle that results in oxidative stress (the pathway is fully explained in Frenis etal. (2021b)). It should be noted that the majority of studies investigating noiseinduced redox imbalance in animals used extremely high sound pressure levels, which try to mimic aircraft noise exposure rather than road traffic noise (Molina etal. 2016), and both loudness and other characteristics (frequency and pattern) may determine detrimental noise effects (Münzel etal. 2017). Moreover, animal studies are not always reliable predictors of human outcomes (Bracken 2009)." Human studies Evidence from human field studies also suggests that oxidative stress plays an important role in noisederived health effects. The administration of the antioxidant Vitamin C diminished endothelial dysfunction associated with train and aircraft noise exposure (Schmidt etal. 2013; Herzog etal. 2019). In a study published in 2020, the authors reported heightened activity in the amygdala among individuals residing in areas with high road traffic noise (Osborne etal. 2020). The amygdala, a part of the limbic system, is responsible for emotional responses, including fear, anxiety, and aggression. It also processes physiological and behavioural reactions to stress and plays a crucial role in the brain’s response to environmental stressors including noise (Spreng 2000; Powell-Wiley etal. 2021). Increased amygdalar activity is linked to a higher risk of CVD due to increased atherosclerotic inflammation (Osborne etal. 2022). In fact, higher noise exposure predicts major adverse cardiovascular events (MACE) and is associated with increased arterial inflammation (Osborne etal. 2020). Recently, the same researchers demonstrated that the combination of air pollution and road traffic noise also contributes to an increased risk of MACE and arterial inflammation (Osborne etal. 2022). According to observational cohort studies, long-term exposure to road traffic noise induces alterations in blood biochemistry and immune response in adults, including elevated levels of IL-12 and high-sensitivity C-reactive protein (hsCRP) or a reduced NKT cell population (Cai etal. 2017; Kim etal. 2017; Kupcikova etal. 2021). However, it is worth noting that these findings were not uniform across all studies (Michaud etal. 2022). Interestingly, the Swiss SAPALDIA cohort concluded that DNA methylation was associated with long-term exposure to road traffic noise and air pollution. This association was linked to pathways related to inflammation, cellular development, and immune responses (Eze etal. 2020). 46825Environmental Science and Pollution Research (2024) 31:46820–46839 As previously noted, ROS are vital for the regulation of several signalling pathways that are linked to numerous health effects. Hence, the upcoming section provides a comprehensive overview of how inflammation and oxidative stress act as mediators of non-auditory health outcomes induced by road traffic noise. Noise‑induced health effects The state of chronic stress resulting from road traffic noise exposure, characterized by alterations in the HPA axis and stress hormones, systemic inflammation, and oxidative stress, can affect various systems and contribute to a wide range on non-auditory diseases (Fig.1). In this review, we focus on its effects on the circadian dysregulation, metabolic alterations, aging and age-related diseases, changes in the gut microbiome, vascular dysfunction, and mental health outcomes. Summary of the main findings explained in this section is available in Table1, where both animal and human studies are presented. Noise andmetabolic alterations Road traffic noise has been suggested to alter metabolic homeostasis and is mainly associated with diabetes mellitus. As previously stated, noise induces changes in the HPA axis, prompting the release of cortisol and other stress hormones, potentially resulting in metabolic disturbances (Babisch 2003). Metabolic alterations are also positively correlated with sleep disorders and circadian disruptions (Depner etal. 2014; Smiley etal. 2019), and these alterations have been associated with noise (Basner and McGuire 2018). Human studies A WHO expert review found that there is still a limited number of publications exploring the connection between road traffic noise and metabolic changes, and the existing results are inconsistent. Therefore, evidence for the risk of getting type-2 diabetes mellitus in response to traffic noise is of low quality (van Kempen etal. 2018). However, more recent studies have observed a positive association between the risk of type-2 diabetes mellitus development and road traffic noise (Ohlwein etal. 2019; Liu etal. 2023), and even long-term exposure to combined noise sources (Sørensen etal. 2023). Animal studies Animal studies also support the idea that noise induces metabolic alterations, with several studies showing that noise exposure provokes alterations in blood biochemistry, diabetes, and insulin resistance in mice (Liu etal. 2016; Morakinyo etal. 2019). Notably, in these experiments, high-noise exposures were used, which may be far from real road traffic noise exposure characteristics. Table1 resumes noise exposure characteristics used in animal studies: high intensity (around 85–100dB) noises, exposed during a certain time, repeated several times. Road traffic noise, however, is usually more constant and with lower intensity. It has to be noted that road traffic noise levels could reach even higher levels in some cities, most of them Asian cities (United Nations 2022). Thus, noise exposures used during animal experiments are similar to aircraft noise: high intensity, intermitted noises, usually separated by a noise-free period (Basner etal. 2017). Although evidence regarding the link between road traffic noise exposure, metabolic alterations, and type-2 diabetes mellitus remains unclear, existing studies imply a potential mechanistic connection involving annoyance, sleep disturbances, alterations in the HPA axis, and the release of stress hormones. Noise could impact glucose metabolism by promoting liver glucose production, decreasing glucose absorption, encouraging fat breakdown in adipocytes, and inhibiting insulin secretion. These effects can result in insulin resistance and inflammation, both linked to diabetes development (Sharma and Singh 2020). In addition, metabolic alterations, abnormal lipid profiles, and insulin resistance are risk factors for CVD (Ormazabal etal. 2018). Noise andmicrobiome In recent years, there has been a significant surge in research investigating the link between gut microbiota and various diseases. Furthermore, the relationship between inflammation, redox signaling, and the gastrointestinal microbiome has been elucidated (Frenis etal. 2021b). Stress has the ability to influence these gastro-intestinal microorganisms, as circulating concentrations of glucocorticoids and catecholamines can modulate microbial growth (Karl etal. 2018). It has to be noted that changes in gut microbiota are associated with several diseases, such as cardiometabolic diseases, neuroinflammation, and neurodegenerative disorders (Collins etal. 2012; Jones and Neish 2017; Campbell and Colgan 2019; Mou etal. 2022), which are also associated with road traffic noise (Münzel etal. 2021; Hahad etal. 2022). Animal studies Although few studies have focused on noise exposure and the microbiome, decreased gut microbiota diversity and compositional alterations were observed in mice exposed to high-noise for 4h per day for 30 consecutive days (Cui etal. 2016, 2018). Another study discovered that disruptions in the gut microbiota were associated with an imbalance between oxidative and anti-oxidant pathways, reduced tight junction protein levels in the intestine and hippocampus, and systemic inflammation triggered by noise 46826 Environmental Science and Pollution Research (2024) 31:46820–46839 Table 1 Summary of the main findings regarding the noise-induced non-auditory health outcomes Health outcome Main finding Human/animal model Noise exposure Reference Stress hormones Increased salivary or urinary cortisol levels in participants under higher road traffic noise exposure Human Road traffic noise Hohmann etal. (2013) No association between road traffic noise and salivary cortisol Human Road traffic noise Wallas etal. (2018) Bloemsma etal. (2021) No association between residential exposure to road traffic noise and hair cortisol concentration Human Road traffic noise Verheyen etal. (2021) Inflammation Increased immune function was observed after 3-day noise exposure and decreased immune function after 28days of exposure Mice 90dB, 5h/day, 3 or 28days Zheng and Ariizumi (2007) Increased levels of IL-6 Mice 85dB during 43s, 69 repetitions Münzel etal. (2017) Pro-inflammatory phenotype and the activation of circulating leukocytes were avoided in Nox2 knockout mice Mice 85dB during 43s, 69 repetitions Eckrich etal. (2021) Exposure to road traffic noise causes increased levels of IL-12 and high-sensitivity C-reactive protein (hsCRP) levels, and decreased NKT cell population Human Road traffic noise Cai etal. (2017); Kim etal. (2017); Kupcikova etal. (2021) Long-term exposure to road traffic noise and air pollution was associated with the enrichment of pathways related to inflammation, cellular development, and immune responses Human Road traffic noise Eze etal. (2020) 46827Environmental Science and Pollution Research (2024) 31:46820–46839 Table 1 (continued) Health outcome Main finding Human/animal model Noise exposure Reference Oxidative stress Increased hippocampal activity of antioxidant enzymes in animals exposed to acute noise, while activity was decreased in chronically exposed ones Rats 100dB, 4h/day, 30days Manikandan etal. (2006) Increased expression of NOX-2 Mice 85dB during 43s, 69 repetitions Münzel etal. (2017) Neuroinflammation, cerebral oxidative stress, or circadian dysregulation due to aircraft noise exposure were avoided in Nox2 knockout mice Mice 85dB during 43s, 69 repetitions Kröller-Schön etal. (2018) Antioxidant Vitamin C diminished noise-exposure induced endothelial dysfunction Human Train noise Aircraft noise Herzog etal. (2019); Schmidt etal. (2013) Metabolic alteration Noise causes metabolic alterations, induces alterations in blood biochemistry, diabetes, and insulin resistance Mice 95dB, 4h/day, 20days 400–3600Hz (dB not defined) Liu etal. (2016, 2018); Morakinyo etal. (2019) Changes in gut microbiome Probiotic treatment alleviated anxiety-like behaviour in noise exposed rats, by restoring functioning of HPA axis and gut-brainmicrobiota axes Rats 95dB, 4h/day, 30days Hadizadeh etal. (2019) Promoting gut microbiota homeostasis with Lactobacillus rhamnosus GG improved gut bacterial balance Rats 20–20,000Hz ( dB not defined) Li etal. (2023a, b) Decreased gut microbiota diversity and compositional alterations were observed after noise exposure for 4h/d during 30 consecutive days Mice 400–3600Hz (dB not defined) Cui etal. (2016, 2018) 46828 Environmental Science and Pollution Research (2024) 31:46820–46839 Table 1 (continued) Health outcome Main finding Human/animal model Noise exposure Reference Imbalance between oxidative and anti-oxidant pathways and systemic inflammation in response to noise were related with alterations in gut microbiota Mice 20–20kHz (98 dB, 4 h/ day,30 days) Chi etal. (2021) Vascular dysfunction Cardiovascular dysfunction Exposure to aircraft noise caused endothelial dysfunction, increased blood pressure, increased levels of neurohormones, and higher sensitivity to vasoconstrictors, including endothelin-1 and noradrenalin. Reduction in NO bioavailability was observed, due to eNOS uncoupling/dysfunction and NO reaction with superoxide in an oxidative state Mice 85dB during 43s, 69 repetitions Kröller-Schön etal. (2018); Münzel etal. (2017) Offsetting upregulation eNOS mRNA levels and main enzymes responsible for eNOS cofactor Mice 85dB during 43s, 69 repetitions Münzel etal. (2017) Road traffic noise exposure caused endothelial dysfunction markers of inflammation and oxidative stress Human Train noise Aircraft noise Aircraft noise Herzog etal. (2019); Schmidt etal. (2015); Schmidt etal. (2013) Cerebrovascular dysfunction Reduced dendritic count in the hippocampus and increased oxidative stress in the frontal cortex after exposure to noise Rats 100dB, 4h/day, 30days Manikandan etal. (2006) Exposure to noise caused hippocampal alterations that could underlie behavioural effects Rats 95–97dB, 2h/day, Single day/five consecutive days Uran etal. (2012) Noise-induced hippocampal oxidative stress and changes in aminoacidergic neurotransmitters Rats 95–97dB, 2h/day, Single day/15 consecutive days Molina etal. 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