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. 2022 Oct;101(10):102063.
doi: 10.1016/j.psj.2022.102063. Epub 2022 Jul 26.

Chronic heat stress causes liver damage via endoplasmic reticulum stress-induced apoptosis in broilers

Bingbing Ma  1 , Tong Xing  1 , Jiaolong Li  2 , Lin Zhang  1 , Yun Jiang  3 , Feng Gao  4
Affiliations

Chronic heat stress causes liver damage via endoplasmic reticulum stress-induced apoptosis in broilers

Bingbing Ma et al. Poult Sci. 2022 Oct.

Abstract

Liver is a central metabolic organ, which is sensitive to heat stress. Liver damage affects animals' health and endangers the livestock and poultry industry. This study aimed to investigate the mechanism of chronic heat stress-induced liver damage in broiler chickens. Broilers were divided into 3 treatments: normal control group (NOR, 22°C), heat stress group (HS, 32°C) and pair-feeding group (PF, 22°C) for a 7-d and 14-d trial. The results showed that 7 d heat exposure caused microvesicular steatosis and reduced glutamine synthetase activity in broiler liver (P < 0.05). After 14 d of heat exposure, heat stress caused vacuolar degeneration and apoptosis in the liver; elevated liver relative weight and liver glutaminase activity as well as plasma ammonia level (P < 0.05). Additionally, heat stress enhanced GRP78 protein expression and the mRNA expressions of endoplasmic reticulum (ER) stress responses genes and apoptosis-related genes in broiler liver after 14 d of heat exposure (P < 0.05). In conclusion, chronic heat stress triggered ER stress-induced apoptosis and caused liver damage, which may compromise ammonia detoxification in broiler liver.

Keywords: broiler; endoplasmic reticulum stress; heat stress; liver apoptosis.

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Figures

Figure 1
Figure 1
Effect of chronic heat stress on the relative weight of liver and blood ammonia level in broiler. The data is presented as mean ± SE (n = 6). a,b-Different letters manifest that there was significant difference among three groups (P < 0.05). Abbreviations: HS, heat-stress group; NOR, normal control group; PF, pair-feeding group.
Figure 2
Figure 2
Effect of chronic heat stress on the histopathological changes in broiler liver (H&E stain; scale bar: 50 µm). Abbreviations: 7d NOR, 7 d of heat exposure, normal control group; 14d NOR, 14 d of heat exposure, normal control group; 7d HS, 7 d of heat exposure, heat stress group; 14d HS, 14 d of heat exposure, heat stress group; 7d PF, 7 d of heat exposure, pair-feeding group; 14d PF, 14 d of heat exposure, pair-feeding group.
Figure 3
Figure 3
Effect of chronic heat stress on the mRNA expressions of GRP78 (A), PERK (B), EIF2A (C), ATF4 (D), ATF6 (E), IRE1 (F), XBP1 (G) in broiler liver. The data is presented as mean ± SE (n = 6). a-c-Different letters manifest that there was significant difference among three groups (P < 0.05). Abbreviations: ATF4, activated transcription factor 4; ATF6, activated transcription factor 6; EIF2A, elongation initiation factor 2 alpha; GRP78, glucose-regulated protein 78; HS, heat-stress group; NOR, normal control group; IRE1, Inositol-requiring enzyme 1; PERK, protein kinase RNA-like ER kinase; PF, pair-feeding group; XBP1, X-box binding protein 1.
Figure 4
Figure 4
Effect of chronic heat stress on the mRNA expressions of CHOP (A), Caspase3 (B), and Bcl-2 (C) in broiler liver. Abbreviations: CHOP, transcriptional factor C/EBP homologous protein; Caspase-3, caspase-3; Bcl-2, B-cell CLL/lymphoma 2; HS, heat-stress group; NOR, normal control group; PF, pair-feeding group. The data is presented as mean ± SE (n = 6). a-c-Different letters manifest that there was significant difference among three groups (P < 0.05).
Figure 5
Figure 5
Effect of chronic heat stress on the protein expressions of GRP78 in broiler liver. Abbreviations: GRP78, glucose-regulated protein 78; HS, heat-stress group; NOR, normal control group; PF, pair-feeding group. The data is presented as mean ± SE (n = 6). a,b-Different letters manifest that there was significant difference among three groups (P < 0.05).
Figure 6
Figure 6
Effect of chronic heat stress on liver apoptotic rate in broiler (TUNEL assay, × 200). Abbreviations: HS, heat-stress group; NOR, normal control group; PF, pair-feeding group. Normal cell nucleus is blue, and apoptotic cells was dyed green. The data is presented as mean ± SE (n = 6). a,b-Different letters manifest that there was significant difference among three groups (P < 0.05).
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