Association between heat stress and oxidative stress in poultry; mitochondrial dysfunction and dietary interventions with phytochemicals

Abstract

Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement of heat stress in inducing oxidative stress has received much interest. Oxidative stress is defined as the presence of reactive species in excess of the available antioxidant capacity of animal cells. Reactive species can modify several biologically cellular macromolecules and can interfere with cell signaling pathways. Furthermore, during the last decade, there has been an ever-increasing interest in the use of a wide array of natural feed-delivered phytochemicals that have potential antioxidant properties for poultry. In light of this, the current review aims to (1) summarize the mechanisms through which heat stress triggers excessive superoxide radical production in the mitochondrion and progresses into oxidative stress, (2) illustrate that this pathophysiology is dependent on the intensity and duration of heat stress, (3) present different nutritional strategies for mitigation of mitochondrial dysfunction, with particular focus on antioxidant phytochemicals. Oxidative stress that occurs with heat exposure can be manifest in all parts of the body; however, mitochondrial dysfunction underlies oxidative stress. In the initial phase of acute heat stress, mitochondrial substrate oxidation and electron transport chain activity are increased resulting in excessive superoxide production. During the later stage of acute heat stress, down-regulation of avian uncoupling protein worsens the oxidative stress situation causing mitochondrial dysfunction and tissue damage. Typically, antioxidant enzyme activities are upregulated. Chronic heat stress, however, leads to downsizing of mitochondrial metabolic oxidative capacity, up-regulation of avian uncoupling protein, a clear alteration in the pattern of antioxidant enzyme activities, and depletion of antioxidant reserves. Some phytochemicals, such as various types of flavonoids and related compounds, were shown to be beneficial in chronic heat-stressed poultry, but were less or not effective in non-heat-stressed counterparts. This supports the contention that antioxidant phytochemicals have potential under challenging conditions. Though substantial progress has been made in our understanding of the association between heat stress and oxidative stress, the means by which phytochemicals can alleviate oxidative stress have been sparsely explored.

Keywords: Antioxidant enzymes; Avian uncoupling protein; Electron transport chain; Flavonoids; Heat Stress; Mitochondrion; Oxidative stress; Poultry.

Fig. 1

Mitochondrial energy transduction and patho-physiology of oxidative stress upon heat stress. Mitochondrial electron transport chain (ETC.; C I, complex I; C II, complex II; Q, coenzyme Q; C III, complex III; cyt c, cytochrome c; C IV, complex IV), ATP synthase (coupling through oxidative phosphorilation) and uncoupling mechanisms (non-protein or protein, by avian uncoupling protein, avUCP or A nucleotide translocator, ANT, catalyzed proton leak) are shown. In the initial phase of acute HS the mitochondrial substrate oxidation (tricarboxylic acid cycle and/or β-oxidation) and ETC. activity are increased resulting in more reduced state of the electron carriers of the ETC. and an increase of ΔѰ resulting in elevated superoxide production (O₂°⁻), while during the later stage of acute HS, downregulation of avUCP worsens the oxidative stress. Chronic HS, however, leads to downsizing the mitochondrial metabolic oxidative capacity, upregulation of avUCP and a clear alteration in the pattern of antioxidant enzyme activities. Superoxide is readily dismutated by superoxide dismutase, SOD (CuZnSOD in intermembrane space and MnSOD in matrix) to give hydrogen peroxide (H₂O₂). H₂O₂ functions as the common ROS messenger in cell signaling due to its constant production, relative stability and diffusion properties. The primary targets of ROS for cell signaling are cysteine residues and protein bound metals, including heme iron. In cell signaling, downstream cascades will effect the activity of transcription factors of which AP-1, NF-kB and Nrf2 have been shown to be affected under HS conditions in poultry. Upon oxidative stress, an overflow of H₂O₂ can either be controlled by catalase (CAT; low affinity, high reactivity) and/or the glutathione-peroxidase/glutathione system (GSH-Px/GSH; high affinity, low reactivity) or undergo further reduction to yield the extremely reactive and dangerous hydroxyl radical (OH°) (Fenton reaction), possibly causing major damage to cellular biomolecules