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Pregnancy is extremely vulnerable to external environmental influences. Bisphenol A, an endocrine-disrupting chemical, poses a significant environmental hazard to individuals of all ages and stages, particularly during pregnancy. The placenta is a temporary organ facilitating the connection between the mother and fetus. While it can detoxify certain exogenous substances, it is also vulnerable to the impacts of endocrine disruptors. Likewise, the intestinal flora is highly sensitive to exogenous stresses and environmental pollutants. The regulation of gut microbiota plays a crucial role in ensuring the health of both the mother and the fetus. The gut-placental axis connects the gut, gut microbes, placenta, and fetus. Exploring possible effects on placental function and fetal development involves analyzing changes in gut microbiota composition. Given that bisphenol A may cross the intestine and affect intestinal function, gut microorganisms, and their metabolites, as well as its potential impact on the placenta, resulting in impaired placental function and fetal development, this study aims to establish a link between bisphenol A exposure, intestinal microorganisms, placental function, and fetal development. This paper seeks to analyze the effects of maternal exposure to bisphenol A during pregnancy on the balance of the maternal gut microbiota, placental function, and fetal development, considering the key role of the gut-placental axis. Additionally, this paper proposes potential directions for future research emphasizing the importance of mitigating the adverse outcomes of bisphenol A exposure during pregnancy in both human and animal studies.
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The endoplasmic reticulum (ER) is a complex and dynamic organelle that initiates unfolded protein response (UPR) and endoplasmic reticulum stress (ER Stress) in response to the accumulation of unfolded or misfolded proteins within its lumen. Autophagy is a paramount intracellular degradation system that facilitates the transportation of proteins, cytoplasmic components, and organelles to lysosomes for degradation and recycling. Preeclampsia (PE) and intrauterine growth retardation (IUGR) are two common complications of pregnancy associated with abnormal trophoblast differentiation and placental dysfunctions and have a major impact on fetal development and maternal health. The intricate interplay between ER Stress, and autophagy and their impact on pregnancy outcomes, through mediating trophoblast differentiation and placental development, has been highlighted in various reports. Autophagy controls trophoblast regulation through a variety of gene expressions and signalling pathways while excessive ER Stress triggers downstream apoptotic signalling, culminating in trophoblast apoptosis. This comprehensive review delves into the intricacies of placental development and explores the underlying mechanisms of PE and IUGR. In addition, this review will elucidate the molecular mechanisms of ER Stress and autophagy, both individually and in their interplay, in mediating placental development and trophoblast differentiation, particularly highlighting their roles in PE and IUGR development. This research seeks to the interplay between ER Stress and impaired autophagy in the placental trophoderm, offering novel insights into their contribution to pregnancy complications.
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BACKGROUND: Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. RESULTS: Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. CONCLUSIONS: Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.
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Compuestos de Bencidrilo , Microbioma Gastrointestinal , Enfermedades Mitocondriales , Fenoles , Humanos , Embarazo , Ovinos , Femenino , Animales , Ratones , Placenta , Retardo del Crecimiento Fetal/inducido químicamente , Retardo del Crecimiento Fetal/metabolismo , Disbiosis/inducido químicamente , Disbiosis/metabolismo , Aceite de Maíz/metabolismo , Estrés Oxidativo , Enfermedades Mitocondriales/metabolismoRESUMEN
This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17ß-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P < 0.05) in the RES + ARG or RES + NCG group than in the RES group. The mRNA expression levels of inducible nitric oxide synthase (iNOS) and solute carrier family 15, member 1 (SLC15A1) were increased (P < 0.05) while those of progesterone receptor (PGR) and fibroblast growth factor 2 (FGF2) were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group. The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport, and reduces the expression of angiogenic growth factor genes and steroid anabolism, leading to better fetal development.
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BACKGROUND: Exposure to bisphenol A (BPA), an environmental pollutant known for its endocrine-disrupting properties, during gestation has been reported to increase the risk of fetal growth restriction (FGR) in an ovine model of pregnancy. We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta, oxidative stress, inflammatory responses, autophagy and endoplasmic reticulum stress (ERS). However, precise mechanisms underlying the BPA-induced placental dysfunction, and subsequently, FGR, as well as the potential involvement of placental ERS in these complications, remain to be investigated. METHODS: In vivo experiment, 16 twin-pregnant (from d 40 to 130 of gestation) Hu ewes were randomly distributed into two groups (8 ewes each). One group served as a control and received corn oil once a day, whereas the other group received BPA (5 mg/kg/d as a subcutaneous injection). In vitro study, ovine trophoblast cells (OTCs) were exposed to 4 treatments, 6 replicates each. The OTCs were treated with 400 µmol/L BPA, 400 µmol/L BPA + 0.5 µg/mL tunicamycin (Tm; ERS activator), 400 µmol/L BPA + 1 µmol/L 4-phenyl butyric acid (4-PBA; ERS antagonist) and DMEM/F12 complete medium (control), for 24 h. RESULTS: In vivo experiments, pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency, progesterone (P4) level and fetal weight, and an increase in placental estrogen (E2) level, together with barrier dysfunctions, OS, inflammatory responses, autophagy and ERS in type A cotyledons. In vitro experiment, the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy, ERS, pro-apoptosis and inflammatory response, and a decrease in the P4 level and the related protein and gene expressions of antioxidant, anti-apoptosis and barrier function. Moreover, treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine (the increased E2 level and decreased P4 level), OS, inflammatory responses, autophagy, and ERS. However, treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above. CONCLUSIONS: In general, the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs, and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine, OS, inflammatory responses, and autophagy. These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.
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Bisphenol A (BPA)-induced oxidative stress (OS) and its potentially associated autophagy and apoptosis have not been studied previously in pregnant ewes. Accordingly, this study investigated the underlying mechanisms of BPA-induced autophagy and apoptosis in the placenta and primary trophoblasts of pregnant ewes exposed to BPA both in vivo and in vitro. In vivo experiment, pregnant Hu ewes (n = 8) were exposed to 5 mg/kg/d of BPA compared to control ewes (n = 8) receiving only corn oil from day 40 through day 110 of gestation. Exposure to BPA during gestation resulted in placental insufficiency, fetal growth restriction (FGR), autophagy, endoplasmic reticulum stress (ERS), mitochondrial dysfunction, OS, and apoptosis in type A placentomes. Regarding in vitro model, primary ovine trophoblasts were exposed to BPA, BPA plus chloroquine (CQ; an autophagy inhibitor) or BPA plus rapamycin (RAP; an autophagy activator) for 12 h. Data illustrated that exposure to BPA enhanced autophagy (ULK1, Beclin-1, LC3, Parkin, and PINK1), ERS (GRP78, CHOP10, ATF4, and ATF6) and apoptosis (Caspase 3, Bcl-2, Bax, P53) but decreased the antioxidant (CAT, Nrf2, HO-1, and NQO1)-related mRNA and protein expressions as well as impaired the mitochondrial function. Moreover, treatment with CQ exacerbated the BPA-mediated OS, mitochondrial dysfunction, apoptosis, and ERS. On the contrary, RAP treatment counteracted the BPA-induced trophoblast dysfunctions mentioned above. Overall, the findings illustrated that BPA exposure could contribute to autophagy in the ovine placenta and trophoblasts and that autophagy, in turn, could alleviate BPA-induced apoptosis, mitochondrial dysfunction, ERS, and OS. These results offer new mechanistic insights into the role of autophagy in mitigating BPA-induced placental dysfunctions and FGR.
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Retardo del Crecimiento Fetal , Placenta , Humanos , Animales , Embarazo , Ovinos , Femenino , Placenta/metabolismo , Retardo del Crecimiento Fetal/inducido químicamente , Apoptosis , Estrés Oxidativo , AutofagiaRESUMEN
Previous studies have revealed that dietary N-carbamylglutamate (NCG) or L-arginine (Arg) improves small intestinal integrity and immune function in suckling Hu lambs that have experienced intrauterine growth retardation (IUGR). Whether these nutrients alter redox status and apoptosis in the colon of IUGR lambs is still unknown. This study, therefore, aimed at investigating whether dietary supplementation of Arg or NCG alters colonic redox status, apoptosis and endoplasmic reticulum (ER) stress and the underlying mechanism of these alterations in IUGR suckling Hu lambs. Forty-eight 7-d old Hu lambs, including 12 with normal birth weight (4.25 ± 0.14 kg) and 36 with IUGR (3.01 ± 0.12 kg), were assigned to 4 treatment groups (n = 12 each; 6 males and 6 females) for 3 weeks. The treatment groups were control (CON), IUGR, IUGR + Arg and IUGR + NCG. Relative to IUGR lambs, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content, as well as proliferation index, were higher (P < 0.05) whereas reactive oxygen species (ROS), malondialdehyde (MDA) levels and apoptotic cell numbers were lower (P < 0.05) in colonic tissue for both IUGR + Arg and NCG lambs. Both mRNA and protein levels of C/EBP homologous protein 10 (CHOP10), B-cell lymphoma/leukaemia 2 (Bcl-2) -associated X protein (Bax), apoptosis antigen 1 (Fas), activating transcription factor 6 (ATF6), caspase 3, and glucose-regulated protein 78 (GRP78) were lower (P < 0.05) while glutathione peroxidase 1 (GPx1), Bcl-2 and catalase (CAT) levels were higher (P < 0.05) in colonic tissue for IUGR + Arg and IUGR + NCG lambs compared with IUGR lambs. Based on our results, dietary NCG or Arg supplementation can improve colonic redox status and suppress apoptosis via death receptor-dependent, mitochondrial and ER stress pathways in IUGR suckling lambs.
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The aquafeed industry continues to expand in response to the rapidly growing aquaculture sector. However, the identification of alternative protein sources in aquatic animal diets to replace conventional sources due to cost and sustainability issues remains a major challenge. Recently, insects have shown tremendous results as potential replacers of fishmeal in aquafeed. The present study aimed to review the utilization of insects in aquafeeds and their effects on aquatic animals' growth and feed utilization, immune response and disease resistance, and fish flesh quality and safety. While many insect species have been investigated in aquaculture, the black soldier fly (Hermetia illucens), and the mealworm (Tenebrio molitor) are the most studied and most promising insects to replace fishmeal in aquafeed. Generally, insect rearing conditions and biomass processing methods may affect the product's nutritional composition, digestibility, shelf life and required insect inclusion level by aquatic animals. Also, insect-recommended inclusion levels for aquatic animals vary depending on the insect species used, biomass processing method, and test organism. Overall, while an appropriate inclusion level of insects in aquafeed provides several nutritional and health benefits to aquatic animals, more studies are needed to establish optimum requirements levels for different aquaculture species at different stages of development and under different culture systems.
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Our previous studies have revealed that dietary N-carbamylglutamate (NCG) and L-arginine (Arg) supplementation improves redox status and suppresses apoptosis in the colon of suckling Hu lambs with intrauterine growth retardation (IUGR). However, no studies have reported the function of Arg or NCG in the colonic microbial communities, barrier function, and inflammation in IUGR-suckling lambs. This work aimed to further investigate how dietary Arg or NCG influences the microbiota, barrier function, and inflammation in the colon of IUGR lambs. Forty-eight newborn Hu lambs of 7 d old were assigned to four treatment groups (n = 12 per group; six male, six female) as follows: CON (normal birth weight, 4.25 ± 0.14 kg), IUGR (3.01 ± 0.12 kg), IUGR + Arg (2.99 ± 0.13 kg), and IUGR + NCG (3.03 ± 0.11 kg). A total of 1% Arg or 0.1% NCG was supplemented in a basal diet of milk replacer, respectively. Lambs were fed the milk replacer for 21 d until 28 d after birth. Compared to the non-supplemented IUGR lambs, the transepithelial electrical resistance (TER) was higher, while fluorescein isothiocyanate dextran 4 kDa (FD4) was lower in the colon of the NCG- or Arg-supplemented IUGR lambs (p < 0.05). The IUGR lambs exhibited higher (p < 0.05) colonic interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and malondialdehyde (MDA) levels than the CON lambs; the detrimental effects of IUGR on colonic proinflammatory cytokine concentrations and redox status were counteracted by dietary Arg or NCG supplementation. Both IUGR + Arg and IUGR + NCG lambs exhibited an elevated protein and mRNA expression of Occludin, Claudin-1, and zonula occludens-1 (ZO-1) compared to the IUGR lambs (p < 0.05). Additionally, the lipopolysaccharide (LPS) concentration was decreased while the levels of acetate, butyrate, and propionate were increased in IUGR + Arg and IUGR + NCG lambs compared to the IUGR lambs (p < 0.05). The relative abundance of Clostridium, Lactobacillus, and Streptococcus was lower in the colonic mucosa of the IUGR lambs than in the CON lambs (p < 0.05) but was restored upon the dietary supplementation of Arg or NCG to the IUGR lambs (p < 0.05). Both Arg and NCG can alleviate colonic barrier injury, oxidative stress (OS), and inflammation by the modulation of colonic microbiota in IUGR-suckling lambs. This work contributes to improving knowledge about the crosstalk among gut microbiota, immunity, OS, and barrier function and emphasizes the potential of Arg or NCG in health enhancement as feed additives in the early life nutrition of ruminants.
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Environmental cadmium (Cd) exposure has been associated with severe liver injury. In contrast, melatonin (Mel) is a candidate drug therapy for Cd-induced liver injury due to its diverse hepatoprotective activities. However, the precise molecular mechanism by which Mel alleviates the Cd-induced liver injury, as well as the Mel-gut microbiota interaction in liver health, remains unknown. In this study, mice were given oral gavage CdCl2 and Mel for 10 weeks before the collection of liver tissues and colonic contents. The role of the gut microbiota in Mel's efficacy in alleviating the Cd-induced liver injury was evaluated by the gut microbiota depletion technique in the presence of antibiotic treatment and gut microbiota transplantation (GMT). Our results revealed that the oral administration of Mel supplementation mitigated liver inflammation, endoplasmic reticulum (ER) stress and mitophagy, improved the oxidation of fatty acids, and counteracted intestinal microbial dysbiosis in mice suffering from liver injury. It was interesting to find that neither Mel nor Cd administration induced any changes in the liver of antibiotic-treated mice. By adopting the GMT approach where gut microbiota collected from mice in the control (CON), Cd, or Mel + Cd treatment groups was colonized in mice, it was found that gut microbiota was involved in Cd-induced liver injury. Therefore, the gut microbiota is involved in the Mel-mediated mitigation of ER stress, liver inflammation and mitophagy, and the improved oxidation of fatty acids in mice suffering from Cd-induced liver injury.
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Cadmium (Cd) is a major environmental stressor that induces fetal growth restriction (FGR). Also, changes in gut microbiome diversity-which can be modulated positively by melatonin (Mel) have implications on fetal development and placental functions. Therefore, this study aimed to explore whether the role of Mel in counteracting the Cd-induced FGR by regulating placental barrier injury, endoplasmic reticulum stress (ERS) and mitophagy in pregnant mice is mediated-in part- via the gut microbiota modulations. Pregnant mice were intraperitoneally injected with CdCl2 (5 mg/kg) and Mel (5 mg/kg) once daily, respectively, at the same time from gestational day (GD) 8 to GD18, and then the maternal colon and placental tissues were collected for detection. To investigate the inner relationship between intestinal flora and the protection of Mel on FGR caused by Cd, gut microbiota transplantation (GMT) was carried out from GD0 to GD18 after the removal of intestinal microbiota by antibiotics. Results indicated that Mel relieved barrier injury, ERS and mitophagy in the placenta, and reversed the maternal gut microbiota dysbiosis. The GMT approach suggested a role of intestinal microbiota in placental barrier injury, ERS and mitophagy induced by Cd. Overall, the results highlighted that the intestinal microbiota and gut-placental axis play a central role in the protective effect of Mel against Cd-induced FGR.
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Microbioma Gastrointestinal , Melatonina , Animales , Cadmio/toxicidad , Femenino , Retardo del Crecimiento Fetal/inducido químicamente , Humanos , Melatonina/farmacología , Melatonina/uso terapéutico , Ratones , Placenta , EmbarazoRESUMEN
Objective: The objectives of this research are to overcome the limitations of rice bran (RB) and de-oiled rice bran (DORB) by fermentation anaerobically using inoculum from the rumen of a canulated sheep for desirable chemical changes. Materials and Methods: Initially, RB and DORB were fermented by 10% rumen liquor for 12 h at 39°C at different moisture levels (10, 20, 30, 40, 50, and 60% phosphate buffer). Again, DORB was fermented for 24, 48, and 72 h at 39°C using 10% rumen liquor at different moisture levels (10, 20, 30, 40, 50, and 60% phosphate buffer). Before and after fermentation, RB and DORB were analyzed for pH, proximate components, neutral detergent fiber (NDF), total-P, inorganic-P, and phytate-P. Results: Fermentation of RB and DORB for 12 h reduced (p < 0.05) pH, crude fiber (CF),NDF, and phytate-P, but increased (p < 0.05) the content of inorganic-P. Subsequent fermentation of DORB for 24, 48, and 72 h reduced pH, CF, and NDF. Total-P of fermented DORB remained similar till 72 h fermentation (p < 0.05). But, inorganic-P increased with the increasing duration (24, 48, and 72 h) of fermentation and increased (30, 40, and 50) moisture level (p < 0.05). Alternatively, phytate-P decreased with increasing duration and moisture level (p < 0.05). Conclusion: Inoculation of rumen microbes and incubation of RB (12 h) and DORB (24 h) at room temperature reduced phytate-P and fiber content (CF and NDF) when the moisture level was up to 50%; those are the indicators to reduce the limitation of RB and DORB to use as feed for non-ruminant animals like poultry and pigs.
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This study aimed to explore whether dietary rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation (IUGR) in ovine fetuses. On d 35 of pregnancy, twin-bearing Hu ewes (n = 32) were randomly assigned to 4 treatment groups (8 ewes and 16 fetuses per group) and fed diets containing 100% of the NRC requirements (CON), 50% of the NRC requirements (RES), RES + RP-Arg (20 g/d) (RESA), or RES + NCG (5 g/d) (RESN). At 08:00 on d 110 of gestation, fetal blood and liver tissue samples were collected. The levels of triglyceride, free fatty acid, cholesterol and ß-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower (P < 0.05) than those of the RES group, but were higher (P < 0.05) than those of the CON group. The interleukin (IL)-6 and IL-1 levels in fetal blood and liver tissue as well as the myeloid differentiation primary response 88 (MyD88), transforming growth factor ß (TGFß), and nuclear factor kappa B (NF-κB) mRNA levels in the fetal liver were decreased (P < 0.05) by the NCG or RP-Arg supplementation compared to the RES treatment. Similarly, the toll-like receptor (TLR)-4, MyD88, TGFß, and p-c-Jun N-terminal kinase (JNK) protein levels in the fetal liver were reduced (P < 0.05) in the NCG and RP-Arg -supplemented groups compared to the RES group. These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism, down-regulating the TLR-4 and the inflammatory JNK and NF-κB signaling pathways, and decreasing cytokine production in ovine fetal blood and liver tissue.
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The objective of this study was to investigate the effects of dietary administration of l-arginine (Arg) or N-carbamylglutamate (NCG) on hepatic energy status and mitochondrial functions in suckling Hu lambs with intrauterine growth retardation (IUGR). Forty-eight newborn Hu lambs of 7 d old were allocated into 4 treatment groups of 12 lambs each, in triplicate with 4 lambs per replicate (2 males and 2 females) as follows: CON (lambs of normal birth weight, 4.25 ± 0.14 kg), IUGR (3.01 ± 0.12 kg), IUGR + 1% Arg (2.99 ± 0.13 kg), or IUGR + 0.1% NCG (3.03 ± 0.11 kg). The experiment lasted for 21 d, until d 28 after birth, and all lambs were fed milk replacer as a basal diet. Compared with IUGR lambs, NCG or Arg administration increased (P < 0.05) the adenosine triphosphate (ATP) level and the activities of complexes I/III/IV, isocitrate dehydrogenase and citrate synthase in the liver. Compared with CON lambs, the relative mRNA levels of adenosine monophosphate-activated protein kinase α1 (AMPKα1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) and transcription factor A (TFAM) were increased (P < 0.05) in the liver of IUGR lambs, but were decreased (P < 0.05) in the liver of NCG- or Arg-treated lambs compared with those in the IUGR lambs. Compared with IUGR lambs, NCG or Arg administration decreased (P < 0.05) the total AMPKα (tAMPKα)-to-phosphorylated AMPKα (pAMPKα) ratio and the protein expression of PGC1α and TFAM. The results suggested that dietary Arg or NCG supplements improved hepatic energy status and mitochondrial function and inhibited the AMPK-PGC1α-TFAM pathway in IUGR suckling lambs.
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OBJECTIVE: Bioactive compounds in ruminant products are related to functional compounds in their diets. Therefore, this study aimed to explore the effect of forage sources, Italian ryegrass (IR) silage vs corn silage (CS) in the total mixed ration (TMR), on milk production, milk composition, and phytanic acid content in milk, as well as on the extent of conversion of dietary phytol to milk phytanic acid. METHODS: Phytanic acid content in milk was investigated for cows fed a TMR containing either IR silage or CS using 17 cows over three periods of 21 days each. In periods 1 and 3, cows were fed CS-based TMR (30% CS), while in period 2, cows were fed IR silage-based TMR (20% IR silage and10% CS). RESULTS: The results showed that there were no differences in fat, protein, lactose, solidsnot-fat, somatic cell count, and fatty acid composition of milk among the three experimental periods. There were no differences in the plasma concentration of glucose, triglycerides, total cholesterol, and nonesterified fatty acids among the three experimental periods, while the blood urea nitrogen was higher (p<0.05) in period 2. The milk phytanic acid content was higher (p<0.05) in period 2 (13.9 mg/kg) compared with periods 1 (9.30 mg/kg) and 3 (8.80 mg/kg). Also, the phytanic acid content in the feces was higher (p<0.05) in period 2 (1.65 mg/kg dry matter [DM]) compared with period 1 (1.15 mg/kg DM), and 3 (1.17 mg/kg DM). Although the phytol contents in feces did not differ among the three feeding periods, the conversion ratio from dietary phytol to milk phytanic acid was estimated to be only 2.6%. CONCLUSION: Phytanic acid content in cow's milk increases with increasing phytol content in diets. However, phytol might not be completely metabolized in the rumen and phytanic acid, in turn, might not be completely recovered into cow's milk. The change of phytanic acid content in milk may be positively correlated with the change of phytol in the diet within a short time.
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This study was aimed at elucidating the protective effects of 18ß-glycyrrhetinic acid (18ßGA) against acrylamide (Acr)-induced cellular damage in diabetic rats. Rats were randomly assigned into eight groups (n = 8) following 12 h of fasting: control group, a single dose of 50 mg/kg streptozotocin (STZ) intraperitoneally (diabetic group), 50 mg/kg 18ßGA orally after 2 weeks from STZ injection (18ßGA group), 20 mg/kg Acr after 1month from STZ injection (Acr group), STZ plus Acr (STZ-Acr group), STZ plus 18ßGA (STZ-18ßGA group), Acr plus 18ßGA (Acr-18ßGA group), or STZ plus Acr plus 18ßGA (STZ-Acr-18ßGA group). Administration of 18ßGA alone increased GSH, GSH-PX, SOD, and CAT in both liver and kidneys. While STZ injection was associated with diabetic and oxidative stress changes as indicated by the higher serum glucose, cholesterol, creatinine, IL-1ß, IL-6, TNF-α, and antioxidant enzyme activities, together with increased lipid peroxides and decreased antioxidant biomarkers in the liver and kidneys. Similarly, the co-administration of STZ and Acr was associated with similar, more augmented effects, compared to STZ alone. The administration of 18ßGA normalized STZ and Acr-induced elevations in oxidative defense variables in the liver and kidney tissues and blood biomarkers. Thus, our study demonstrated that the damaging effects of Acr were more exaggerated in diabetic rats. Furthermore, it showed the ability of 18ßGA to inhibit reactive oxygen species generation and restore the antioxidant defenses in diabetic rats with Acr-induced liver and kidney cytotoxicity.
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Diabetes Mellitus Experimental , Ácido Glicirretínico , Acrilamida/toxicidad , Animales , Antioxidantes , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacología , Estrés Oxidativo , RatasRESUMEN
BACKGROUND: Previous studies demonstrated that dietary l-arginine (Arg) alters the equilibrium between reactive oxygen species (ROS) generation and biological defenses to resist oxidant-induced toxicity. Whether supplying Arg can protect ovine intestinal epithelial cells (OIECs) from hydrogen peroxide (H2O2)-induced oxidative damage is unclear. OBJECTIVES: The current study aimed to examine the effect of Arg on mitophagy, mitochondrial dysfunction, and apoptosis induced by H2O2 in OIECs. METHODS: The OIECs were incubated in Arg-free DMEM supplemented with 100 µM Arg (CON) or 350 µM Arg (ARG) alone or with 150 µM H2O2 (CON + H2O2, ARG + H2O2) for 24 h. Cellular apoptosis, mitochondrial function, autophagy, and the related categories of genes and proteins were determined. All data were analyzed by ANOVA using the general linear model procedures of SAS (SAS Institute) for a 2 × 2 factorial design. RESULTS: Relative to the CON and ARG groups, H2O2 administration resulted in 44.9% and 26.5% lower (P < 0.05) cell viability but 34.7% and 61.8% greater (P < 0.05) ROS concentration in OIECs, respectively. Compared with the CON and CON + H2O2 groups, Arg supplementation led to 40.7% and 28.8% lower (P < 0.05) ROS concentration but 14.9%-49.0% and 29.3%-64.1% greater (P < 0.05) mitochondrial membrane potential, relative mitochondrial DNA content, and complex (I-IV) activity in OIECs, respectively. Compared with the CON and CON + H2O2 groups, Arg supplementation led to 33.9%-53.1% and 22.4%-49.1% lower (P < 0.05) mRNA abundance of proapoptotic genes, respectively. Relative to the CON and CON + H2O2 groups, Arg supplementation resulted in 33.0%-59.2% and 14.6%-37.7% lower (P < 0.05) abundance of proapoptotic, mitophagy, and cytoplasmic cytochrome c protein, respectively. CONCLUSIONS: Supply of Arg protects OIECs against H2O2-induced damage partly by improving mitochondrial function and alleviating cellular apoptosis and autophagy.
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Arginina/farmacología , Mucosa Intestinal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Células Cultivadas , ADN Mitocondrial/metabolismo , Suplementos Dietéticos , Peróxido de Hidrógeno/toxicidad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitofagia/efectos de los fármacos , Sustancias Protectoras/farmacología , Proteínas/metabolismo , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , OvinosRESUMEN
The current work aimed at investigating the effects of the dietary supplementation of N-carbamylglutamate (NCG) or l-arginine (Arg) on the duodenal mitophagy, mitochondrial function, inflammation, and barrier function in suckling lambs suffering from intrauterine-growth-retardation (IUGR). Forty-eight neonate Hu lambs were used in this study: 12 lambs with normal birth weight (NBW: 4.25 ± 0.14 kg) and 36 lambs with IUGR (3.01 ± 0.13 kg). Seven day old lambs were assigned to 4 treatment groups (12 lambs in each group) as follows: control group (CON), IUGR group, IUGR + Arg, and IUGR + NCG. Lambs were fed the experimental diets for 21 days from 7 days to 28 days of age. Compared with IUGR lambs, the Arg or NCG-treated IUGR lambs had a markedly higher duodenal transepithelial electrical resistance (TER) and lower fluorescein isothiocyanate dextran (FD4) (P < 0.05), respectively. The duodenal mitochondrial membrane potential change (ΔΨm), relative mitochondrial DNA (mtDNA) content, adenosine triphosphate (ATP) level, together with the activities of the respiratory complexes I, III, and IV were markedly higher in Arg or NCG-treated IUGR lambs than those in non-supplemented IUGR lambs (P < 0.05). The expressions of the integrity-related proteins (occludin and zonula occludens-1 (ZO-1)), antioxidant- and apoptosis-related proteins (B-cell lymphoma/leukaemia 2 (Bcl2), superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPx1)), and the nitric oxide-dependent pathway-related proteins (epithelial NO synthase (eNOS) and inducible NO synthase (iNOS)) were higher in NCG or Arg-supplemented IUGR lambs than those in nontreated IUGR lambs (P < 0.05). The duodenal expressions of the mitophagy-related proteins (microtubule-associated protein light chain 3 (LC3) I, LC3 II, Belin1, PTEN induced putative kinase 1 (PINK1), and Parkin) and the immune function-related proteins (myeloid differentiation factor 88 (MyD88), IL-6, nuclear factor kappa B (p65), toll-like receptor (TLR4) and TNF-α) were reduced (P < 0.05) in NCG or Arg-supplemented IUGR lambs compared with non-supplemented IUGR lambs. These results demonstrated that the dietary supplementation of Arg or NCG enhanced the duodenal barrier function and mitochondrial function, mitigated duodenal inflammation, and suppressed mitophagy in suckling lambs suffering from IUGR.
Asunto(s)
Alimentación Animal , Arginina , Suplementos Dietéticos , Retardo del Crecimiento Fetal/dietoterapia , Glutamatos , Ovinos/crecimiento & desarrollo , Animales , Animales Lactantes , Distribución AleatoriaRESUMEN
BACKGROUND: In nonruminants, many of the biological roles of l-arginine (Arg) at the intestinal level are mediated through the Arg-nitric oxide (Arg-NO) pathway. Whether the Arg-NO pathway is involved in controlling the immune response and viability in ovine intestinal epithelial cells (IOECs) is unclear. OBJECTIVES: The current study aimed to examine the role of the Arg-NO pathway in apoptosis, antioxidant capacity, and mitochondrial function of IOECs. METHODS: The IOECs were incubated in Arg-free DMEM supplemented with 150 µM Arg (CON) or 300 µM Arg (ARG) alone or with 350 µM Nw-nitro-l-arginine methyl ester hydrochloride (l-NAME) (CON + NAME, ARG + NAME) for 24 h. The reactive oxygen species (ROS) concentration, antioxidant capacity, and cell apoptotic percentage were determined. RESULTS: Arg supplementation decreased (P < 0.05) the ROS concentration (38.9% and 22.7%) and apoptotic cell percentage (57.2% and 54.8%) relative to the CON and CON + NAME groups, respectively. Relative to the CON and ARG treatments, the l-NAME administration decreased (P < 0.05) the mRNA abundance of superoxide dismutase 2 (32% and 21.3%, respectively) and epithelial NO synthase (36% and 29.1%, respectively). Arg supplementation decreased (P < 0.05) the protein abundance of apoptosis antigen 1 (FAS) (52.0% and 43.9%) but increased (P < 0.05) those of nuclear respiratory factor 1 (31.3% and 22.9%) and inducible NO synthase (35.2% and 41.8%) relative to the CON and CON + NAME groups, respectively. CONCLUSIONS: The inhibition of apoptosis in IOECs due to the increased supply of Arg is associated with the mitochondria- and FAS-dependent pathways through the activity of the Arg-NO pathway. The findings help elucidate the role of the Arg-NO pathway in IOEC growth and apoptosis.
Asunto(s)
Arginina/farmacología , Células Epiteliales/efectos de los fármacos , Mucosa Intestinal/citología , Óxido Nítrico/metabolismo , Animales , Apoptosis , Arginina/metabolismo , Células Cultivadas , Regulación de la Expresión Génica/fisiología , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/farmacología , OvinosRESUMEN
L-arginine (Arg) is a semiessential amino acid with several physiological functions. N-Carbamylglutamate (NCG) can promote the synthesis of endogenous Arg in mammals. However, the roles of Arg or NCG on hepatic inflammation and apoptosis in suckling lambs suffering from intrauterine growth restriction (IUGR) are still unclear. The current work is aimed at examining the effects of dietary Arg and NCG on inflammatory and hepatocyte apoptosis in IUGR suckling lambs. On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 432 twin lambs. Normal-birthweight and IUGR Hu lambs were allocated randomly (n = 12/group) to control (CON), IUGR, IUGR+1% Arg, or IUGR+0.1% NCG groups. Lambs were fed for 21 days from 7 to 28 days old. Compared with CON lambs, relative protein 53 (P53), apoptosis antigen 1 (Fas), Bcl-2-associated X protein (Bax), caspase-3, cytochrome C, tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB) p65, and NF-κB pp65 protein levels were higher (P < 0.05) in liver from IUGR lambs, whereas those in liver from IUGR lambs under Arg or NCG treatment were lower than those in IUGR lambs. These findings indicated that supplementing Arg or NCG reduced the contents of proinflammatory cytokines at the same time when the apoptosis-related pathway was being suppressed, thus suppressing the IUGR-induced apoptosis of hepatic cells.