Effects of betaine on viability, apoptosis, function protein expression and oxidative status in heat-stressed IEC-6 cells.

Intestinal epithelial dysfunction is one of the key factors in the pathogenesis of heat stress-induced disease. The purpose of this experiment was to investigate whether betaine protects IEC-6 cells from dysfunction induced by heat stress (HS) through antioxidative mechanism. The IEC-6 cells were divided into four groups: control group incubated at 37 °C, while those in heat treated groups (41 °C for 24 h) were pretreated with 0, 0.5 and 1 mmol/L betaine, respectively. Cell viability, apoptosis, barrier function protein and oxidative status were analyzed. Compared to control group, the rate of apoptosis and the Bax and caspase-3 expressions significantly increased in HS group (P < 0.05), however, cell activity, total antioxidative capacity (T-AOC), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and the expression of Bcl-2, claudin-1 and occludin decreased significantly (P < 0.05). Betaine (0.5 mmol/L) can significantly enhance IEC-6 cell viability, while significantly reduce the apoptosis rate of cell during HS (P < 0.05). Meanwhile, the expression of Bcl-2, claudin-1 and occludin proteins were also significantly upregulated (P < 0.05) when compared to HS group. HS had a negative impact on IEC-6 cells, while betaine protected from damage caused by HS via increasing the antioxidative capacity. This suggested that betaine might be an effective dietary additive to protect animals from detrimental intestinal reactions caused by HS.

Boron Attenuates Heat Stress-Induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress in Mouse Granulosa Cells.

Heat stress-induced apoptosis in granulosa cells is mediated by multiple apoptotic signaling pathways, including endoplasmic reticulum (ER) stress. Boron is a naturally occurring trace element with several cytoprotective properties. Nonetheless, the molecular mechanisms involved in the protective functions of boron in granulosa cells undergoing apoptosis caused by heat stress (HS) remain unclear. In this study, we investigated the role of boric acid, a predominant chemical form of boron, in HS-induced apoptotic damage in mouse granulosa cells (mGCs) and explored the underlying mechanisms. We found that HS treatment suppressed cell viability; increased the apoptotic rate of cells; potentiated the activity of caspase-3, a key player in the caspase-mediated apoptotic signaling pathway; and activated ER stress markers, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) in mGCs. However, boric acid treatment effectively alleviated the effects of both HS-induced and thapsigargin (an ER stress agonist)-induced apoptosis, such as the enhanced activity of caspase-3 and increase in GRP78 and CHOP expression. Moreover, treatment with 4-phenylbutyrate (4-PBA), an ER stress antagonist, significantly attenuated these HS-induced adverse effects in mGCs. In addition, boric acid supplementation in the culture medium significantly restored the decreased estradiol levels in heat-treated mGCs. The administration of boric acid to female mice previously exposed to hyperthermal conditions effectively restored the levels of serum estradiol in vivo. Collectively, these findings suggest that HS induces apoptosis in mGCs via ER stress pathways and that boron has a protective effect against these adverse effects. This study provides novel insights into the benefits of using boron against heat-induced apoptosis.

Characterization of heat stress affecting the growth performance, blood biochemical profile, and redox status in male and female broilers at market age.

This study investigated the effects of acute heat stress (HS), sex, and their interaction on growth performance, serum biochemical and redox status in the later stage broilers. Two hundred 38-day-old Ross 308 chicks were allocated in a factorial arrangement of 2 × 2 (temperatures and sexes) with 5 replicates of 10 bird each. Thermoneutral and heat-stressed broilers were raised at 24 ± 1 °C or 32 ± 1 °C from day 38 to 39, respectively. HS decreased the average daily feed intake (ADFI) and average daily gain (ADG) whereas it increased feed conversion ratio (FCR), rectal temperature (RT), and respiratory rate (RR) in broilers exposed to high temperature for 24 h and 48 h. Moreover, RT, RR, serum glucose, and HDL-C levels increased while triglyceride (TG), total superoxide dismutase (T-SOD), and glutathione peroxidase (GPx) decreased in broilers exposed to high temperature for 12 h. Male broilers had higher final body weight (FBW), ADFI, ADG, total protein carbonyl group, and lower FCR and T-SOD than females in HS condition for 24 h and 48 h. Lower RT, serum albumin, HDL-C, activities of T-SOD and GPx were observed when compared with those of males in HS condition for 12 h. There were significant temperature × sex interactive effects on ADFI, ADG, and TG in broilers exposed to high temperature for 24 h and 48 h. The present study suggests that the acute HS negatively affects growth performance which is accompanied by the disorder of serum nutritional metabolism and imbalance of redox status in later stage broilers. Some parameters presented sexual differences that suggested it may be more effective to alleviate the negative effects of HS when broiler producers take into account the gender of broiler.

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes.

Heat stress (HS) causes testicular injury, resulting in decreased fertility. Alpha-lipoic acid (ALA) is a well-known antioxidant. The aim of this study was to investigate the protective effects of ALA on HS-induced testicular damage in chickens. Histological changes; biomarkers of oxidative stress, including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA); markers of endoplasmic reticulum (ER) stress, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP); apoptosis-related modulators, including Bax, Bcl-2, and caspase 3, in testicular tissue and serum testosterone levels were evaluated in chickens under heat stress. Heat stress induces spermatogenic cell abnormalities in chicken testes. Compared to the HS group, the histomorphological abnormalities in testicular tissue were visibly ameliorated, with significant increases in the enzyme activities of GPx, SOD, and CAT, increased serum testosterone concentration, and decreased MDA levels in the ALA + HS group. Consistent with these results, compared with the HS group, the protein levels of GRP78, CHOP, caspase 3, and Bax were significantly decreased, whereas Bcl-2, StAR, and 3ß-HSD protein levels were increased in the ALA + HS group. Collectively, these findings suggest that ALA significantly ameliorates the heat-induced histomorphological abnormalities in the testes and decreased testosterone production by potentiating the activities of anti-oxidative enzymes (GPx, SOD, and CAT), inhibiting ER stress-related apoptotic pathways (Bax, Bcl-2, and caspase 3), and increasing steroidogenic gene (StAR and 3ß-HSD) expression in chickens.

Selenium Attenuates Chronic Heat Stress-Induced Apoptosis via the Inhibition of Endoplasmic Reticulum Stress in Mouse Granulosa Cells.

Heat stress induces apoptosis in various cells. Selenium, an essential micronutrient, has beneficial effects in maintaining the cellular physiological functions. However, its potential protective action against chronic heat stress (CHS)-induced apoptosis in granulosa cells and the related molecular mechanisms are not fully elucidated. In this study, we investigated the roles of selenium in CHS-induced apoptosis in mouse granulosa cells and explored its underlying mechanism. The heat treatment for 6-48 h induced apoptosis, potentiated caspase 3 activity, increased the expression levels of apoptosis-related gene BAX and ER stress markers, glucose-regulated protein 78 (GRP78), and CCAAT/enhancer binding protein homologous protein (CHOP) in mouse granulosa cells. The treatment with ER stress inhibitor 4-PBA significantly attenuated the adverse effects caused by CHS. Selenium treatment significantly attenuated the CHS- or thapsigargin (Tg, an ER stress activator)-induced apoptosis, potentiation of caspase 3 activity, and the increased protein expression levels of BAX, GRP78, and CHOP. Additionally, treatment of the cells with 5 ng/mL selenium significantly ameliorated the levels of estradiol, which were decreased in response to heat exposure. Consistently, administering selenium supplement alleviated the hyperthermia-caused reduction in the serum estradiol levels in vivo. Together, our findings indicate that selenium has protective effects on CHS-induced apoptosis via inhibition of the ER stress pathway. The current study provides new insights in understanding the role of selenium during the process of heat-induced cell apoptosis.