The challenges of maintaining oxidative balance for migratory birds
During energetically-challenging periods, all aerobic organisms must contend with an increased production of reactive species (RS) by either neutralizing the RS with antioxidants to minimize resulting oxidative damage, or damage must be restored using repair mechanisms (Halliwell and Gutteridge 2007, Costantini 2014, 2019). Long-distance flight increases metabolism (Swanson 2010, Corder and Schaeffer 2015, DeMoranville et al. 2019, Bishop, C.M., Guglielmo 2022) and poses a potential oxidative challenge for flying animals (McWilliams et al. 2021, McWilliams, S.R., Ramenofsky, M., Pierce 2022). For example, Nathusius’ bats Pipistrellus nathusii that were captured and sampled during a migratory flight had higher circulating oxidative damage markers compared to individuals that were captured and rested for 18-24 hours (Costantini et al. 2018). Similarly, circulating protein damage and the antioxidant enzyme glutathione peroxidase (GPx) were higher in European robins Erithacus rubecula during a nocturnal migratory flight compared to resting individuals caught during the day, indicating that damage to muscle occurs with flight and the antioxidant system can respond rapidly (Jenni-Eiermann et al. 2014). These acute effects of flight were also demonstrated in captive Yellow-rumped warblers (Setophaga coronata coronate) , as protein carbonyls and superoxide dismutase (SOD) activity were higher in the pectoralis muscle immediately after a flight in a wind tunnel compared to individuals at rest (Dick and Guglielmo 2019). Similarly, flight-trained zebra finchesTaeniopygia guttata had increased circulating oxidative damage compared to untrained sedentary individuals (Skrip et al. 2016). These studies together demonstrate that migratory bats and birds respond to such oxidative challenges by increasing antioxidant enzyme activities, depleting or augmenting non-enzymatic antioxidant capacity, and in these cases increasing oxidative damage. They also reveal that too little is known about tissue-specific oxidative status of migratory birds (Dick and Guglielmo 2019) and the extent to which an individual’s circulating oxidative status reflects the oxidative state of muscles and organs at a given time (Costantini 2019, Frawley et al. 2021a). What remains to be determined for migratory songbirds is how the oxidative status of different tissues and plasma responds to both flight training and ecologically-relevant differences in diet quality (i.e. antioxidants and fat composition).
Certain dietary fats challenge the antioxidant system - Birds rely primarily on fatty acids to fuel flight (Guglielmo, 2018; McWilliams, Guglielmo, Pierce, & Klaassen, 2004), and several species of migratory songbirds increase the amounts of unsaturated fats and especially long-chain polyunsaturated fats (PUFAs) in their diet, fat stores and in circulation during migration compared to non-migration periods (Pierce et al. 2004, Pierce and McWilliams 2005, Price et al. 2008, Smith and McWilliams 2010, Jensen et al. 2020, McWilliams, S.R., Ramenofsky, M., Pierce 2022). The potential benefits of consuming certain long-chain PUFA (e.g., 18:2n-6 PUFA) including enhanced efficiency of energy metabolism during exercise and reduced flight costs (Pierce and McWilliams 2014, Guglielmo 2018), are also associated with potential oxidative costs because PUFA are highly susceptible to oxidative damage (Halliwell and Gutteridge 2007, Skrip and McWilliams 2016, McWilliams et al. 2020). The resulting lipid radicals often cause a self-perpetuating chain reaction damaging nearby PUFAs and other molecules (Halliwell and Gutteridge 2007, Skrip and McWilliams 2016, Cooper-Mullin et al. 2019). Birds preferentially consuming 18:2n-6 PUFA during migration to enhance their metabolism (Pierce and McWilliams 2014) likely require an augmented antioxidant system to protect against the oxidative challenge that such PUFAs pose (McWilliams et al. 2021).
Dietary antioxidants augment the antioxidant system - Many songbird species select fruits that are high in antioxidants and fat during fall (post-breeding) migration, suggesting that antioxidant consumption may be important to protect against oxidative damage during this life history stage (Alan and McWilliams 2013, Bolser et al. 2013). Water-soluble antioxidants such as anthocyanins are preferentially consumed by certain songbird species during fall migration and in cafeteria-style choice experiments (Schaefer et al. 2008, Alan et al. 2013, Bolser et al. 2013). Anthocyanins are potent antioxidants (Halliwell and Gutteridge 2007) that are exclusively stable at acidic pH levels (i.e. they degrade extensively in less than an hour at pH 7.4) and are more likely to remain intact and absorbed in the 2 orders of magnitude more acidic stomachs of songbirds (pH 2) relative to mammals (pH 4.4) (Dangles and Fenger 2018). Anthocyanins can directly or indirectly affect the antioxidant system and also have been shown to protect birds from an immune challenge (Catoni et al. 2008) and protect against some of the metabolic costs associated with flight training (Casagrande et al. 2020) as well as courtship (Carbeck et al. 2018) and reproduction in spring (Frawley et al. 2021b). These energy savings associated with consuming anthocyanins may allow birds to invest in increasing enzymatic or non-enzymatic antioxidants to prevent damage (McWilliams et al. 2020). Non-enzymatic antioxidant capacity increases with fat stores in songbirds on stopovers during migration (Costantini et al. 2007, Skrip et al. 2015) and is greatest during the pre-migratory fueling stage in shorebirds (Gutiérrez et al. 2019). Thus, hyperphagia associated with preparation for migration in birds may augment their antioxidant system by increasing fat-soluble antioxidants stored within newly accumulated fat stores or by increasing water-soluble antioxidant metabolites continuously released by gut microbes (Dogan Comert and Gokman 2017).