OxInflammation at High Altitudes: A Proof of Concept from the Himalayas

Mrakic‐Sposta, Simona; Biagini, Denise; Bondi, Danilo; Pietrangelo, Tiziana; Vezzoli, Alessandra; Lomonaco, T; Francesco, Fabio Di; Verratti, Vittore

doi:10.3390/antiox11020368

Cited by 7 publications

(8 citation statements)

References 68 publications

(75 reference statements)

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“…A growing body of evidence indicates that hypoxia decreases both the activity and effectiveness of the antioxidant system, as well as causing increased ROS production with a consequent increase in oxidative damage [ 3 ] to lipids [ 4 , 5 , 6 ], proteins and the DNA [ 5 , 7 ] of cellular compartments [ 8 , 9 , 10 ]. Most studies on the effects of hypoxia have been carried out at high altitude [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. However, under such conditions, several factors other than hypoxia could induce oxidative damage; UV radiation, intense physical activity and cold may in fact produce an imbalance between ROS generation and antioxidant protection [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

The “ON-OFF” Switching Response of Reactive Oxygen Species in Acute Normobaric Hypoxia: Preliminary Outcome

Mrakic‐Sposta

Gussoni

Marzorati

et al. 2023

IJMS

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Exposure to acute normobaric hypoxia (NH) elicits reactive oxygen species (ROS) accumulation, whose production kinetics and oxidative damage were here investigated. Nine subjects were monitored while breathing an NH mixture (0.125 FIO2 in air, about 4100 m) and during recovery with room air. ROS production was assessed by Electron Paramagnetic Resonance in capillary blood. Total antioxidant capacity, lipid peroxidation (TBARS and 8-iso-PFG2α), protein oxidation (PC) and DNA oxidation (8-OH-dG) were measured in plasma and/or urine. The ROS production rate (μmol·min−1) was monitored (5, 15, 30, 60, 120, 240 and 300 min). A production peak (+50%) was reached at 4 h. The on-transient kinetics, exponentially fitted (t1/2 = 30 min r2 = 0.995), were ascribable to the low O2 tension transition and the mirror-like related SpO2 decrease: 15 min: −12%; 60 min: −18%. The exposure did not seem to affect the prooxidant/antioxidant balance. Significant increases in PC (+88%) and 8-OH-dG (+67%) at 4 h in TBARS (+33%) one hour after hypoxia offset were also observed. General malaise was described by most of the subjects. Under acute NH, ROS production and oxidative damage resulted in time and SpO2-dependent reversible phenomena. The experimental model could be suitable for evaluating the acclimatation level, a key element in the context of mountain rescues in relation to technical/medical workers who have not had enough time for acclimatization—as, for example, during helicopter flights.

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Section: Introductionmentioning

confidence: 99%

The “ON-OFF” Switching Response of Reactive Oxygen Species in Acute Normobaric Hypoxia: Preliminary Outcome

Mrakic‐Sposta

Gussoni

Marzorati

et al. 2023

IJMS

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“…Regarding blood redox analyses, as reported, post-trek increases in ROS production rate, NOx, total Hcy, and GSH were detected; conversely, TAC and total Cys and CysGly decreased at Post [ 30 ]. The key result concerning the endocrine system was the impairment of the hypothalamic–hypophyseal axis.…”

Section: Resultsmentioning

confidence: 81%

“…Oxidative stress (OxS) is defined as the excessive production of ROS related to antioxidant defence and can be triggered by endogenous and exogenous factors, among which are expeditions to high altitudes. In fact, exposure to high altitude has been associated with an increase in ROS and related oxidative damage [ 10 , 11 , 30 , 32 ] induced by environmental factors such as hypoxia, cold, UV ray, exposure, and/or physical exercise (daily frequency, low-middle intensity, high volume) [ 30 ]. Moreover, Agarwal et al reported that several extrinsic or environmental factors, such as ionising radiations, alcohol, obesity, deficiencies in antioxidants, varicocele, bacterial/viral infections, toxins, and chemotherapy can induce testicular ROS, causing abnormal spermatogenesis [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

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Fertility Impairment after Trekking at High Altitude: A Proof of Mechanisms on Redox and Metabolic Seminal Changes

Verratti

Mrakic‐Sposta

Fusi

et al. 2022

IJMS

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Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas. Sperm samples were collected before (Pre), 10 days after (Post), and 70 days after the end of the expedition (Follow-up). Sperm concentration, cholesterol and oxysterol membrane content, and redox status were measured. Hypoxic trek led to a significant reduction in sperm concentration (p < 0.001, η2p = 0.91), with a reduction from Pre to Post (71.33 ± 38.81 to 60.65 ± 34.63 × 106/mL) and a further reduction at Follow-up (to 37.13 ± 39.17 × 106/mL). The seminal volume was significantly affected by the hypoxic trek (p = 0.001, η2p = 0.75) with a significant reduction from Pre to Post (2.86 ± 0.75 to 1.68 ± 0.49 mL) and with partial recovery at Follow-up (to 2.46 ± 0.45 mL). Moreover, subjects had an increase in ROS production (+86%), and a decrease in antioxidant capacity (−37%) in the Post period with partial recovery at Follow-up. These results integrated the hormonal response on thyroid function, hypothalamus–pituitary–gonadal axis, and the prolactin/cortisol pathways previously reported. An uncontrolled ROS production, rather than a compromised antioxidant activity, was likely the cause of impaired sperm quality. The reduction in fertility status observed in this study may lie in an evolutionary Darwinian explanation, i.e., limiting reproduction due to the “adaptive disadvantage” offered by the combined stressors of high-altitude hypoxia and daily physical exercise.

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“…Under hypobaric hypoxic conditions, the crosstalk between oxidative stress and inflammation is important. Studies have demonstrated positive feedback between oxidative stress and inflammation, which recently has been coined “oxinflammation” [ 36 , 37 ]. Therefore, based on the mentioned evidence, there is an important role of inflammation under hypoxic conditions that could affect different tissues and organs, including the lung ( Figure 1 ), which will be discussed below.…”

Section: Hypoxia and Inflammationmentioning

confidence: 99%

Inflammation in Pulmonary Hypertension and Edema Induced by Hypobaric Hypoxia Exposure

Alam

Peña

Aguilera

et al. 2022

IJMS

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Exposure to high altitudes generates a decrease in the partial pressure of oxygen, triggering a hypobaric hypoxic condition. This condition produces pathophysiologic alterations in an organism. In the lung, one of the principal responses to hypoxia is the development of hypoxic pulmonary vasoconstriction (HPV), which improves gas exchange. However, when HPV is exacerbated, it induces high-altitude pulmonary hypertension (HAPH). Another important illness in hypobaric hypoxia is high-altitude pulmonary edema (HAPE), which occurs under acute exposure. Several studies have shown that inflammatory processes are activated in high-altitude illnesses, highlighting the importance of the crosstalk between hypoxia and inflammation. The aim of this review is to determine the inflammatory pathways involved in hypobaric hypoxia, to investigate the key role of inflammation in lung pathologies, such as HAPH and HAPE, and to summarize different anti-inflammatory treatment approaches for these high-altitude illnesses. In conclusion, both HAPE and HAPH show an increase in inflammatory cell infiltration (macrophages and neutrophils), cytokine levels (IL-6, TNF-α and IL-1β), chemokine levels (MCP-1), and cell adhesion molecule levels (ICAM-1 and VCAM-1), and anti-inflammatory treatments (decreasing all inflammatory components mentioned above) seem to be promising mitigation strategies for treating lung pathologies associated with high-altitude exposure.

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OxInflammation at High Altitudes: A Proof of Concept from the Himalayas

Cited by 7 publications

References 68 publications

The “ON-OFF” Switching Response of Reactive Oxygen Species in Acute Normobaric Hypoxia: Preliminary Outcome

The “ON-OFF” Switching Response of Reactive Oxygen Species in Acute Normobaric Hypoxia: Preliminary Outcome

Fertility Impairment after Trekking at High Altitude: A Proof of Mechanisms on Redox and Metabolic Seminal Changes

Inflammation in Pulmonary Hypertension and Edema Induced by Hypobaric Hypoxia Exposure

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