Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Abstract

Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

Keywords: Nrf2; antioxidants; oxidative stress; poultry; vitagenes.

Figure 1

Antioxidant defence mechanisms (adapted from Reference [13]).

Figure 2

Oxidative stress and adaptive responses (adapted from Reference [99] with modifications).

Figure 3

Participation of Nrf2 in the AO defence network. In cells under physiological homeostatic conditions, cytosolic transcription factor Nrf2 is kept at low levels being bound to Keap1 by the ubiquitin ligase complex Cullin (Cul)3-RING-box protein (Rbx)1 (Cul3). This complex ubiquitinates Nrf2, triggering its constant proteasomal degradation. Under oxidative stress, ROS modify/oxidise SH-groups within Keap1 leading to conformational changes inducing the Nrf2 release from Keap1. This prevents Nrf2 proteasomal degradation and Nrf2 translocates to the nucleus. In the nucleus, Nfr2 binds to the ARE and initiates the transcription of an array of direct or indirect antioxidant enzymes including SOD, GPx, CAT, GST, GR, GCL, Trx, TrxR, PRDX1, SRDX1, HO-1, NQO1. G6PD, IDH2, etc. These enzymes contribute to the improvement of the antioxidant defence network and reduce the cellular oxidative stress. The Nrf2 induced synthesis of AO enzymes also participates in regulation of stress adaptation and redox signalling. The restoration of cellular homeostasis leads to Nrf2–Keap-1 complex formation and activation of Nrf2 degradation by ubiquitin–proteasome system and decreases the Nrf2 mediated synthesis of AO enzymes.

Figure 4

Hypothetical scheme of Nrf2–NF-κB crosstalk.