Sodium salicylate attenuates lipopolysaccharide (LPS)-induced adipsia, but not hypophagia, in broiler chickens

A study was conducted to determine the influence of sodium salicylate on the behaviour and the food and water consumption of broiler chickens after lipopolysaccharide (LPS) injection. An oral dose of 100 mg/kg sodium salicylate was given and an acute phase reaction in broiler chickens was provoked through the intravenous injection of Escherichia coli LPS. Water intake was higher in the LPS and salicylate-treated group than in the positive control group. The salicylate treatment, however, did not restore the food intake, or influence the behaviour of the chickens. These data show that sodium salicylate has a positive effect on the water intake after intravenous injection of LPS in chickens and suggests that there is a difference in mechanism of action of food and water consumption after LPS injection in chickens.     

Effect of dietary supplementation of astaxanthin from Phaffia rhodozyma on lipopolysaccharide‐induced early inflammatory responses in male broiler chickens (Gallus gallus) fed a corn‐enriched diet

Effect of dietary supplementation of astaxanthin (Ax) from Phaffia rhodozyma on lipopolysaccharide‐induced inflammatory responses was investigated in male broiler chickens fed a corn‐based diet. Birds (1 week of age) were fed a corn‐enriched diet containing either 0 or 100 ppm Ax for 2 weeks and were intraperitoneally injected with lipopolysaccharide (LPS, 1 mg/kg body weight). Inflammatory responses were evaluated by determining changes in expression of messenger RNA (mRNA) in cytokines and mediators related to inflammatory responses (interleukin (IL)‐1 beta and ‐6, inducible nitrite synthase (iNOS), interferon (IFN)‐ γ and cyclooxygenase (Cox)‐2 in the liver and spleen after 2 h of LPS injection and plasma ceruloplasmin concentration as an acute phase protein. Birds fed Ax showed significantly higher iNOS mRNA expression in the liver and spleen compared to that of control birds. Ax‐fed birds also showed greater increase in mRNA expression in the liver of IL‐1, IL‐6 and IFN‐γ compared to that of control birds. The enhancing effect of Ax was further progressed when LPS was injected. No difference was found in plasma ceruloplasmin concentration between the Ax‐fed group and control group. The results suggest that feeding supplementation of Ax (100 ppm) to a corn‐enriched diet possibly does not have anti‐inflammatory effect in male broiler chickens.     

ORIGINAL ARTICLE: Lutein exposure,in ovo or in the diet,reduces parameters of inflammation in the liver and spleen laying‐type chicks (Gallus gallus domesticus)

These trials examined whether the demonstrated effects of embryonic and dietary carotenoid exposure on the inflammatory immune response in fast growing chickens also occur in slow growing chickens. The systemic and local inflammatory responses of chicks were examined in two experiments with two in ovo lutein levels (C+, carotenoid replete; or C?, carotenoid‐deplete), two dietary lutein levels (0 or 40 mg lutein/kg diet), and two inflammatory challenges [no exposure or lipopolysaccharide (LPS)‐vaccinated]. At 24 h after LPS vaccination, spleen weight was not affected by diet or in ovo lutein, but liver weight increased from C+ eggs (p < 0.01), and in LPS‐vaccinated chicks fed 0 mg lutein (p < 0.05), but not in chicks fed 40 mg lutein. Plasma carotenoids and liver carotenoids were reduced post‐LPS (p < 0.05). Splenic IL‐6 mRNA abundance was the greatest post‐LPS in C? chicks fed 40 mg lutein vs. C+ chicks fed 40 mg lutein (p < 0.05). Hepatic IL‐6, iNOS and TGFβ and splenic iNOS and TGFβ were not affected by in ovo or dietary lutein. The systemic and local inflammatory results are similar to those observed in fast growing chickens, and support that lutein‐depleted birds have greater inflammatory responses.     

Effect of lipopolysaccharide infusion on gene expression of inflammatory cytokines in normal horses in vivo

Horses are exquisitely sensitive to bacterial endotoxin and endotoxaemia is common in colic cases. In this study, gene expression of inflammatory cytokines was characterised in the blood of healthy horses following i.v. administration of lipopolysaccharide (LPS). Six horses received an LPS infusion and 6 controls received an equivalent volume of saline. Gene expression of genes encoding interleukin (IL)‐1α, IL‐1β, IL‐6, IL‐8, and tumour necrosis factor‐α (TNF‐α) was quantified by real‐time PCR. Gene expression of all inflammatory cytokines was upregulated following administration of LPS. Interleukin‐1α, IL‐1β, IL‐8 and TNF‐α gene expression peaked at 60 min, while IL‐6 expression peaked at 90 min post LPS infusion. Interleukin‐1β and IL‐6 messenger RNA expression levels were above the baseline values 3 h post LPS infusion, whereas IL‐1α, IL‐8 and TNF‐α expression levels returned to baseline values by 3 h after LPS infusion. It was concluded that LPS infusion upregulated gene expression of inflammatory cytokines in the blood of healthy horses.     

Antipyretic effect of oral sodium salicylate after an intravenous E. coli LPS injection in broiler chickens

A study was set up to investigate the influence of sodium salicylate on fever and acute phase reaction after lipopolysaccharide (LPS) injection in broiler chickens. An acute phase reaction was provoked through the intravenous injection of Escherichia coli LPS. Four oral doses of sodium salicylate were tested. Apart from body temperature, other inflammation indices, such as plasma corticosterone and ceruloplasmin, serum thromboxane B2 and zinc concentrations were monitored. Intravenous LPS induced a fever of about 1 degree C. A dose-dependent attenuation of the fever response of the chickens in the salicylate treated groups was observed. LPS-injected chickens also showed elevated plasma corticosterone and ceruloplasmin, while serum thromboxane and zinc concentrations decreased. Except for thromboxane B2, no linear relationship with increasing salicylate dose could be shown for the other blood variables. These data confirm that sodium salicylate is an effective antipyretic agent after injection of LPS in chickens, if used at an appropriate dosage. No dose-related change could be found for the other inflammation indices.     

Lipopolysaccharide and cytokines modulate leukotriene (LT)B4 and LTC4 production by porcine endometrial endothelial cells

Uterine inflammatory response is mediated by inflammatory mediators including eicosanoids and cytokines produced by immune and endometrial cells. Interactions between lipopolysaccharide (LPS) and cytokines, and leukotrienes (LTs) in endothelium, important for the host defence during the inflammation, are unknown. We studied the effect of LPS, tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐4 and IL‐10 on 5‐lipooxygenase (5‐LO), LTA₄ hydrolase (LTAH) and LTC₄ synthase (LTCS) mRNA and protein expression, LTB₄ and LTC₄ release from porcine endometrial endothelial cells, and cell viability. For 24 hr, cells were exposed to LPS (10 or 100 ng/ml of medium) and cytokines (each 1 or 10 ng/ml). 5‐LO mRNA/protein expression augmented after incubation with larger doses of LPS, TNF‐α, IL‐4 and IL‐10 and smaller dose of IL‐1β. Larger dose of TNF‐α, smaller doses of LPS and IL‐1β and both doses of IL‐10 increased LTAH mRNA/protein expression. LTAH protein content was up‐regulated by larger dose of LPS, but it was reduced in response to both doses of IL‐4. LTCS mRNA expression was elevated by larger doses of LPS, IL‐4 and IL‐10 or both doses of TNF‐α and IL‐1β. LTCS protein level increased after treatment with both doses of IL‐1β, IL‐4 and IL‐10, smaller dose of LPS and larger dose of TNF‐α. Both doses of LPS and larger doses of TNF‐α and IL‐10 increased LTB₄ release. LPS, IL‐1β and IL‐10 at smaller doses, or TNF‐α and IL‐4 at larger doses stimulated LTC₄ release. Smaller doses of TNF‐α and IL‐1β or both doses of IL‐4 enhanced the cell viability. This work provides new insight on the participation of LPS, TNF‐α, IL‐1β, IL‐4 and IL‐10 in LTB₄ and LTC₄ production/release from porcine endometrial endothelial cells, and the effect of above factors on these cells viability. The used cellular model gives the possibility to further establish the interactions between inflammatory mediators.     

Relieving effect of Artemisia argyi aqueous extract on immune stress in broilers

This experiment aimed to investigate the relieving action of Artemisia argyi aqueous extract (AAE) on immune stress in broiler chickens. A 2 × 2 factorial design was used to test the effect of 2 dietary treatments (adding 0 or 1000 mg/kg AAE) and 2 immune stress treatments (injecting saline or lipopolysaccharide (LPS)). A total of 96 one‐day‐old Arbor Acres (AA) broilers were randomly divided into four treatment groups with six replicates, four birds in each replicate. Broilers in Treatment groups 1 and 2 were fed with the basal diet, and those in Treatment groups 3 and 4 were fed with the experimental diet supplemented with 1000 mg/kg AAE. On days 14, 16, 18 and 20, broilers in both Treatments 1 and 3 were injected intra‐abdominally with LPS solution at the dose of 500 μg LPS per kg BW with the LPS dissolved in sterile saline at a concentration of 100 μg/ml, and those in Treatments 2 and 4 were injected intra‐abdominally with equal amount of sterile 0.9% saline. Blood samples were collected on days 21 and 28. The results showed that dietary supplementation of AAE prevented reductions in average daily gain (ADG) and average daily feed intake (ADFI) of broilers caused by LPS on d 15–21. On day 21, the injection of LPS increased serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT); meanwhile, feeding AAE reduced the rise of CORT caused by LPS. Immune parameters such as interleukin‐1 (IL‐1), interleukin‐2 (IL‐2), interleukin‐6 (IL‐6), immunoglobulin G (IgG) and immunoglobulin A (IgA) were also improved by LPS, but the content of IL‐2 and IgG in broilers fed with AAE diet was significantly lower than that of broilers fed with control diet. All the data suggested that diets supplemented with AAE could relieve the immune stress response of broilers.     

Expression of Interleukin (IL)‐1β and IL‐1 Receptors Genes in the Hypothalamus of Anoestrous Ewes after Lipopolysaccharide Treatment

This study was designed to determine the effect of intravenous lipopolysaccharide (LPS) administration on the secretion of interleukin (IL)‐1β and IL‐1 receptors (IL‐1Rs) gene expression in the hypothalamus of anoestrous ewes. Gene expression of IL‐1β and its receptors was assayed by the real‐time polymerase chain reaction. The expression of IL‐1β in the hypothalamus was detected using Western blot. Our results showed that IL‐1β mRNA is transcribed in the ovine hypothalamus. Lipopolysaccharide increased (p ≤ 0.01) the IL‐1β gene expression in the pre‐optic area 2.4‐fold, the anterior hypothalamus (AHA) 3.4‐fold, the medial basal hypothalamus 3.7‐fold and the medial eminence 3.9‐fold. The pro‐form and mature form of IL‐1β protein were found in the hypothalamus after endotoxin injection. In general, the endotoxin also increased more than two times (p ≤ 0.01) the expression of IL‐1 receptor type I (IL‐1R1) and type II (IL‐1R2) genes in the hypothalamus, except the AHA, where the number of IL‐1R2 mRNA was extremely low and not sufficient to the quantitative analysis. These results demonstrate that the peripheral immune/inflammatory challenge increases the IL‐1β expression in the hypothalamus. This endogenous IL‐1β seems to be involved in the modulation of processes which are regulated at the hypothalamic level. One of these processes could be a reproduction.     

Disposition of sodium salicylate,flunixin and meloxicam after intravenous administration in broiler chickens

Three nonsteroidal anti-inflammatory drugs (NSAIDs) [sodium salicylate, flunixin (FLU) and meloxicam (MEL)] were administered intravenously to broiler chickens. Plasma concentrations were determined by high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. After intravenous administration of sodium salicylate (50 mg/kg), FLU (1.1 mg/kg) and MEL (0.5 mg/kg), these drugs were eliminated from plasma with a mean half-life of 04.04, 05.45 and 03.20 h, respectively. Apparent volumes of distribution (0.39, 0.08 and 0.12 L/kg, respectively) indicated that tissue distribution was limited for the three drugs. Total body clearance was 70 mL/h.kg for sodium salicylate and 10 and 25 mL/kg.h for FLU and MEL, respectively. Based on the pharmacokinetic parameters these NSAIDs may offer possibilities for treatment of various conditions in chickens.     

Use of lipopolysaccharide (LPS) as a positive control for the evaluation of immunopotentiating drug candidates in experimental avian colibacillosis models

The aetiologic agent of avian colibacillosis is Escherichia coli. Colibacillosis is a disease that causes mortality and production performance problems in chickens which results in economic losses for the poultry industry. It will be increasingly important for scientists to identify novel solutions that can be implemented which will provide poultry producers with a tool to manage this economically important disease. The purpose of this investigation was to determine whether lipopolysaccharide (LPS) could be used as a positive control to evaluate novel chemistries for immunopotentiator activity in battery or floor-pen avian colibacillosis models in chickens. In the battery study, subcutaneous administration of LPS to one-day-old broiler cockerels caused a significant reduction (P < 0.003) in all parameters of colibacillosis evaluated, i.e. mean air sac lesion scores, per cent air sac lesions, E. coli re-isolation and per cent mortality. However, in the floor-pen study, subcutaneous administration to one-day-old broiler chicks resulted in a numerical, but not statistically significant reduction (P < 0.1) in mortality associated with colibacillosis. These data indicate that LPS can be used as a positive control to evaluate the efficacy of immunopotentiator drug candidates in avian colibacillosis models.     

Pharmacokinetics and bioavailability of valnemulin in broiler chickens

Wang, R., Yuan, L.G., He, L.M., Zhu, L.X., Luo, X.Y., Zhang, C.Y., Yu, J.J., Fang, B.H., Liu, Y.H. Pharmacokinetics and bioavailability of valnemulin in broiler chickens. J. vet. Pharmacol. Therap. 34 , 247–251. The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS). Pharmacokinetic characterization was performed by non‐compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(V_z) of 4.27 ± 0.99 L /kg. Mean valnemulin t_1/2β(h), Cl_β(L /h /kg), V_ss (L /kg) and AUC_(0–∞)(μg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a C_max of 2.2 μg/mL achieved at 0.43 h (t_max), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 μg/mL, 1.54 ± 0.27 h and 74.42%. A multiple‐peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2–6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens.     

Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows

Donalisio, C., Barbero, R., Cuniberti, B., Vercelli, C., Casalone, M., Re, G. Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows. J. vet. Pharmacol. Therap.  36 , 130–139. In this study, ex vivo assays were carried out in dairy cows to evaluate the anti‐inflammatory effects of two nonsteroidal anti‐inflammatory drugs: ketoprofen (KETO) and flunixin meglumine (FM). Twelve healthy Holstein dairy cattle were randomly allocated to two groups (n=6): group 1 received FM and group 2 received KETO at recommended therapeutic dosages. The anti‐inflammatory effects of both drugs were determined by measuring the production of coagulation‐induced thromboxane B₂ (TXB₂), lipopolysaccharides (LPS) (10 μg/mL)‐induced prostaglandin E₂ (PGE₂), and calcium ionophore (60 μm )‐induced leukotrien B₄ (LTB₄). Cytokine production was assessed by measuring tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ) and interleukin‐8 (CXCL8) concentrations after incubation in the presence of 10 μg/mL LPS. The IC₅₀ of FM and KETO was determined in vitro by determining the concentration of TXB₂ and PGE₂ in the presence of scalar drug concentrations (10^?9–10^?3 m ). Both FM and KETO inhibited the two COX isoforms in vitro, but showed a preference for COX‐1. FM and KETO showed similar anti‐inflammatory effects in the cow.     

Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of robenacoxib and ketoprofen in a feline model of inflammation

Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B₂ concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E₂ concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE₂ concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB₂ between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivoIC₅₀COX‐1/IC₅₀COX‐2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.     

Withdrawal time of four pharmaceutical formulations of enrofloxacin in poultry according to different maximum residues limits

San Martin, B., Cornejo, J., Lapierre, L., Iragüen, D., Pérez, F., Hidalgo, H., Andre, F. Withdrawal time of four pharmaceutical formulations of enrofloxacin in poultry according to different maximum residues limits. J. vet. Pharmacol. Therap. 33 , 246–251. To ensure delivery of safe animal products to consumers, the withdrawal time (WDT) of drugs must be respected. Property differences among pharmaceutical formulations, for the same drugs, can lead to differences in the WDTs estimation. The WDTs of four commercial formulations of enrofloxacin (ENRO) in broiler chickens, considering MRLs established by different countries, were studied. Two hundred‐thirty‐four broiler chicks were allotted among four groups; the formulations were orally administered daily with 10 mg/kg bw. After treatment, six chickens of each group and two controls were slaughtered daily until day 9 post‐treatment. Samples of muscle and liver were collected, and analyzed using HPLC‐MS‐MS. The WDTs among formulations of ENRO showed differences of 24 and 48 h. Based on the European Community and Chile MRLs of 100 μg/kg (muscle) and 200 μg/kg (liver), the WDTs did not exceed 5 days. When Japan MRL was considered (10 μg/kg_,), the WDTs increased up to 8 days. These results indicate that for WDTs determination, the differences among pharmaceutical formulations of a drug must be considered as well as the MRLs.     

Dietary L-carnitine supplementation enhances the lipopolysaccharide-induced acute phase protein response in broiler chickens

The objective of the present study was to evaluate the potential effects of dietary L-carnitine supplementation on acute phase protein response upon a lipopolysaccharide (LPS) challenge of male broiler chickens receiving a commercial broiler diet supplemented with 15 or 100 mg L-carnitine/kg or an unsupplemented (control) diet from 14 days of age onwards. At 28 days of age, eight chickens per dietary treatment were weighed and subcutaneously injected with 300 microg LPS from E. coli (100 microg LPS/ml saline) or 3 ml saline (unsupplemented group only). During the next 10 days, blood samples were taken repeatedly and analysed for their hemopexin (HX) and alpha-1 acid glycoprotein (AGP) levels. Extra dietary L-carnitine did not affect broiler performance. At day 1 postinjection, plasma HX and AGP levels were significantly increased in all treatment groups. However, the elevations in circulating HX and AGP levels were more pronounced in the L-carnitine supplemented chickens, especially in the 100mg L-carnitine group. It is concluded that extra L-carnitine in the diet of broiler chickens enhances or advances the acute phase protein response. The exact mode of action needs to be elucidated but seems to be consistent with a glucocorticoid mimicking effect.     

Effect of L‐carnitine on proliferative response and mRNA expression of some of its associated factors in splenic mononuclear cells of male broiler chicks

The effect of L‐carnitine supplementation on mitogen (concanavalin A, Con A) induced proliferation of mononuclear cells (MNC) in the spleen was investigated in broiler chickens at different ages. Day‐old chickens were fed a diet supplemented with or without L‐carnitine (100 ppm) for 24 days. The carnitine‐supplemented group showed greater proliferation of MNC in the spleen in response to Con A than that of the control group at 24 days of age. In addition, at 24 days of age the carnitine‐supplemented group showed higher expression of interleukin (IL)‐2 and interferon (IFN)‐γ mRNA, but lower expression of inducible nitric oxide synthase (iNOS) in the Con A‐stimulated splenic MNC than the control group. The enhancement effect of L‐carnitine on MNC proliferation and IL‐2 mRNA expression was not found in chicks at 14 days of age. Addition of L‐carnitine (50 nmol/mL) to the culture medium enhanced proliferation and IL‐2 mRNA expression of splenic MNC obtained from 24‐day‐old but not from 14‐day‐old broiler chickens. The results suggest that L‐carnitine is capable of enhancing MNC proliferation in broiler chickens at 24 days of age partly through increasing IL‐2 and IFN‐γ production and decreasing NO production.     

Influence of procyanidin supplementation on the immune responses of broilers challenged with lipopolysaccharide

In the present study, the effect of dietary procyanidin (PCA, from pine needles) supplementation on the innate immunity of broilers were investigated. The experiment was designed as a 2 × 4 factorial arrangement (eight cages / treatment; six birds (one‐day‐old) / cage) with dietary PCA concentrations (0, 0.05, 0.075 and 0.1%) and two immune treatments (injection of lipopolysaccharide (LPS) (0.5 mg/kg body weight) or saline). LPS was dissolved in sterile 9 g/L (w/v) NaCl solution at 16, 18, 20 days of age to mimic immune stress. The remaining birds were injected with saline as a placebo. The results indicated that, prior to LPS challenge, the PCA diet had no significant effect on bird growth performance. The injection of LPS was also not associated with any significant changes in poultry performance. LPS injection increased the activity of nitrogen oxides (NOx) and the concentrations of inflammatory cytokines (interferon‐γ (IFN‐γ), interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐6 and IL‐10) in serum; dietary PCA decreased these concentrations (P < 0.05) in the PCA 0.1% group, further illustrating the immune effect of PCA. In conclusion, PCA supplementation has a beneficial effect on LPS challenge, which may be associated with the inhibition of the secretion of cytokines and decrease in the proinflammatory marker NOx.     

Forsythia suspensa extract attenuates lipopolysaccharide‐induced inflammatory liver injury in rats via promoting antioxidant defense mechanisms

Reactive oxygen species (ROS) have been shown to have a role in inflammation. We investigated whether Forsythia suspensa extract (FSE) could exert its antioxidant potential against lipopolysaccharide (LPS)‐induced inflammatory liver injury in rats. Rats were orally fed FSE once daily for 7 consecutive days prior to LPS (Escherichia coli, serotype O55:B5) injection. LPS treatment caused liver dysfunction as evidenced by massive histopathological changes and increased serum alanine aminotransferase and aspartate aminotransferase activities which were ameliorated by FSE pretreatment. FSE attenuated LPS‐induced depletion of cytosolic nuclear factor‐erythroid 2‐related factor 2 (Nrf2) and suppression of Nrf2 nuclear translocation in liver, and the generation of ROS and malondialdehyde in serum and liver. FSE increased the Nrf2‐mediated induction of heme oxygenase‐1 in liver, as well as superoxide dismutase and glutathione peroxidase activities in serum and liver. Importantly, FSE attenuated LPS‐induced nuclear factor‐кB (NF‐кB) nuclear translocation in liver, and subsequently decreased tumor necrosis factor‐α, interleukin (IL)‐1β and IL‐6 levels in serum and liver, which were associated with FSE‐induced activation of Nrf2 in liver. These results indicate that the protective mechanisms of FSE may be involved in the attenuation of oxidative stress and the inhibition of the NF‐кB‐mediated inflammatory response by modulating the Nrf2‐mediated antioxidant response against LPS‐induced inflammatory liver injury.     

Effects of dietary coenzyme Q10 supplementation on hepatic mitochondrial function and the activities of respiratory chain-related enzymes in ascitic broiler chickens

1. One hundred and sixty 1-d-old Arbor Acre male broiler chicks were fed with maize-soybean based diets for 6 weeks in a 2 x 2 factorial experiment. The factors were CoQ10 supplementation (0 or 40 mg/kg) and Escherichia coli lipopolysaccharide (LPS) challenge (LPS or saline). 2. CoQ10 was supplemented from d 1. From d 18, the chickens received three weekly i.p. injections of LPS (1.0 mg/kg BW) or an equivalent amount of sterile saline as control. From d 10 on, all chickens were exposed to low ambient temperature (12 to 15 degrees C) to induce ascites. 3. The blood packed cell volume and ascites heart index of broiler chickens were reduced by dietary CoQ10 supplementation. Mitochondrial State 3 and State 4 respiration, respiratory control ratio and phosphate oxygen ratio were not changed, but H+/site stoichiometry of complex II + III was elevated by dietary CoQ10 supplementation. 4. Cytochrome c oxidase and H+-ATPase activity were increased by CoQ10 supplementation, whereas NADH cytochrome c reductase and succinate cytochrome c reductase were not influenced. Mitochondrial anti-ROS capability was increased and malondialdehyde content was decreased by CoQ10 supplementation. 5. The work suggested that dietary CoQ10 supplementation could reduce broiler chickens' susceptibility to ascites, which might be the result of improving hepatic mitochondrial function, some respiratory chain-related enzymes activities and mitochondrial antioxidative capability.