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

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.

Artificial rearing influences the morphology,permeability and redox state of the gastrointestinal tract of low and normal birth weight piglets

Background： In this study the physiological implications of artificial rearing were investigated. Low（LBW） and normal birth weight（NBW） piglets were compared as they might react differently to stressors caused by artificial rearing. In total, 42 pairs of LBW and NBW piglets from 16 litters suckled the sow until d19 of age or were artificially reared starting at d3 until d19 of age. Blood and tissue samples that were collected after euthanasia at 0, 3, 5, 8 and 19 d of age. Histology, ELISA, and Ussing chamber analysis were used to study proximal and distal small intestine histomorphology, proliferation, apoptosis, tight junction protein expression, and permeability. Furthermore, small intestine,liver and systemic redox parameters（GSH, GSSG, GSH-Px and MDA） were investigated using HPLC.Results： LBW and NBW artificially reared piglets weighed respectively 40 and 33% more than LBW and NBW sowreared piglets at d19（P 〈 0.01）. Transferring piglets to a nursery at d3 resulted in villus atrophy, increased intestinal FD-4 and HRP permeability and elevated GSSG/GSH ratio in the distal small intestine at d5（P 〈 0.05）. GSH concentrations in the proximal small intestine remained stable, while they decreased in the liver（P 〈 0.05）. From d5 until d19, villus width and crypt depth increased, whereas PCNA, caspase-3, occludin and claudin-3 protein expressions were reduced. GSH,GSSG and permeability recovered in artificially reared piglets（P 〈 0.05）.Conclusion： The results suggest that artificial rearing altered the morphology, permeability and redox state without compromising piglet performance. The observed effects were not depending on birth weight.

Effects of Berberine on Hepatic Sirtuin 1-uncoupling Protein 2 Pathway in Non-alcoholic Fatty Liver Disease Rats Induced by High-fat Diet

Objective To investigate the involvement of sirtuin 1（SIRT1）-uncoupling protein 2（UCP2） pathway in the development of non-alcoholic fatty liver disease and whether berberine exerts its effects by regulating this pathway. Methods Male SD rats were divided into three groups： normal control group, high-fat diet group, and berberine supplement group. The rats in the normal control group were given normal diet while the rats in the other two groups were fed with high-fat diet. Rats in the berberine supplement group were concurrently given berberine（100 mg/kg body weight） once daily. After 16 weeks, the levels of serum, liver lipids, and serum aminotransferase were measured using an automatic biochemical analyzer. Superoxide dismutase（SOD） activity and malondialdehyde（MDA） content in the liver were measured using commercial kits. Histopathological changes of liver tissues were observed by hematoxylin and eosin（HE） staining and Oil Red O staining. The hepatic m RNA and protein levels of SIRT1 and UCP2 were assayed by reverse transcription polymerase chain reaction（RT-PCR） or Western blotting. Results Berberine supplement could significantly decrease the serum and liver lipid contents in rats fed with high-fat diet. Meanwhile, SOD level was significantly elevated, but MDA level was reduced in the liver. The results of HE and Oil Red O staining showed that the hepatic steatosis was alleviated in berberine supplement group. Furthermore, berberine induced an increase in SIRT1 expression but a decrease in UCP2 expression. Conclusion The regulation of hepatic SIRT1-UCP2 pathway may be an important mechanism by which berberine exerts the beneficial effects in NAFLD rats.

Yishen Jiangzhuo Granules(益肾降浊冲剂) Affect Tubulointerstitial Fibrosis via A Mitochondrion-Mediated Apoptotic Pathway

Objective： To investigate the effect of Yishen Jiangzhuo Granules （益肾降浊冲剂 , YSJZG） on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure （CRF） rats and explore its mechanism from molecular pathology, gene, protein levels, and relative pathway. Methods： The CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups： sham-operation group, model （CRF） group, Niaoduqing Granules （尿毒清颗粒）-treated group [5 g/（kg.day）], low-, moderate-, and high-dose [L-YSJZG, M-YSJZG, H-YSJZG at 3, 6, and 9 g/（kg-day）] YSJZG-treated group （n=10 each）. The levels of serum creatinine （Scr）, blood urea nitrogen （BUN）, and 24-h urine protein were assessed after 10 weeks of treatment. The tubulointerstitial injury and collagen deposition were evaluated using periodic acid-schiff stain and Masson staining. Renal tubular epithelial cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial injury was observed using an electron microscope, and superoxide dismutase （SOD）, glutathione （GSH） and malondialdehyde （MDA） levels were assessed using chromometry. Transforming growth factor- 1 β（TGF-β 1） expression was assessed using immunohistochemistry. The expressions of Bax, Bcl-2, peroxisome proliferator-activated receptor γ coactivator-1 α （PGC-1α）, mitochondrial transcription factor A （Tfam）, mitogen-activated protein kinases （MAPK） phosphorylation were evaluated by Western blot. Results： YSJZG decreased the 24-h urine protein, BUN, Scr, remnant kidney weight-to-body weight ratio, renal tubular injury, deposition of collagen, and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1 α, up-regulated the expression of Bcl-2, and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF- 13 1 expression, increased SOD and GSH activity, decreased the MDA level, and inhibited p38MAPK and pERK1/2 phosphorylation （all P〈0.01）. Conclusion： YSJZG improved the renal function in rats with CRF and inhibited the progression of tubulointerstitial fibrosis by dose-dependently alleviating mitochondrial injury, restoring the expression of Tfam and PCG-1α , and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.