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Central and peripheral effects of L-citrulline on thermal physiology and nitric oxide regeneration in broilers.

ABSTRACT: The mechanism that mediates L-citrulline (L-Cit) hypothermia is poorly understood, and the involvement of nitric oxide signaling has not been fully elucidated. Therefore, this study aimed to determine L-Cit's influence on body temperature and to ascertain the central and peripheral mechanisms associated with this response. Chicks responded to intracerebroventricular (ICV) injection of L-Cit with high and low body temperatures (P < 0.05) depending on the dose tested, for both the surface and rectal temperatures. Peripheral (i.p.) L-Cit injection did not affect body temperature responses. Nitric oxide (NO) concentration and NO synthase (NOS) were influenced with varying doses of L-Cit. Hypothalamic NO was increased at 4 µg L-Cit whereas, plasma iNOS was elevated at 2µg L-Cit treatment. However, i.p. L-Cit did not change the NO content, rather it induced higher (P < 0.05) plasma tNOS and iNOS activity, and further upregulated iNOS and nNOS gene expression in the hypothalamus. In addition, ICV L-Cit potentiated a pro- versus anti-inflammatory milieu with the induction of IL-8, IL-10, and TGFβ (P < 0.05), which may be related to the changes in body temperature. Following ICV L-Cit administration, it was observed that L-Cit caused dose variable changes in the ultrastructure of hypothalamic neurons. The lowest dose was associated with a higher number of dead or degenerating neurons, whereas the highest L-Cit dose had fewer neuronal numbers with larger sizes. Therefore, this study shows that central and peripheral L-Cit administration imposes changes in body temperature, nitric oxide production, and inflammatory responses, in a dose-dependent manner.

SUBMITTER: Uyanga VA

PROVIDER: S-EPMC8804195 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Central and peripheral effects of L-citrulline on thermal physiology and nitric oxide regeneration in broilers.

Uyanga Victoria Anthony VA Liu Lei L Zhao Jingpeng J Wang Xiaojuan X Jiao Hongchao H Lin Hai H

Poultry science 20211223 3

The mechanism that mediates L-citrulline (L-Cit) hypothermia is poorly understood, and the involvement of nitric oxide signaling has not been fully elucidated. Therefore, this study aimed to determine L-Cit's influence on body temperature and to ascertain the central and peripheral mechanisms associated with this response. Chicks responded to intracerebroventricular (ICV) injection of L-Cit with high and low body temperatures (P < 0.05) depending on the dose tested, for both the surface and rect ...[more]

PMID: 35101686

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Project description:Heat stress (HS) adversely affects several physiological responses in organisms, but the underlying molecular mechanisms involved are yet to be fully understood. L-Citrulline (L-Cit) is a nutraceutical amino acid that is gaining research interest for its role in body temperature regulation and nitric oxide synthesis. This study investigated whether dietary supplementation with L-Cit (1% of basal diet) could ameliorate the effects of acute HS on thermotolerance, redox balance, and inflammatory responses of broilers. Ross 308 broilers (288 chicks) were subjected to two environments; thermoneutral at 24°C (TNZ) or HS at 35°C for 5 h, and fed two diets; control or L-Cit. The results showed that HS increased the ear, rectal (RT), and core body (CBT) temperatures of broilers, along with higher respiratory rate. The RT and CBT readings were intermittently affected with time effect, whereas, L-Cit supplementation lowered the mean CBT than the control diet. Antioxidant assays showed that superoxide dismutase was increased during HS, while, catalase was promoted by L-Cit supplementation. In addition, L-Cit induced glutathione peroxidase activity compared to the control diet during HS. Hypothalamic heat shock protein (HSP)-90 was upregulated by HS, but L-Cit downregulated heat shock factor (HSF)-1, and HSP 60 mRNA expressions. HSF 3 mRNA expression was downregulated by L-Cit under TNZ condition. More so, HS increased the plasma nitric oxide (NO) concentration but lowered the total NO synthase (tNOS) activity. In contrast, L-Cit supplementation limited NO production but increased the tNOS activity. Arginase activity was increased in the control fed group during HS but L-Cit supplementation lowered this effect. The NOS-COX pathway was significantly affected under TNZ condition, since L-Cit supplementation downregulated the mRNA expression of iNOS-COX2 in the hypothalamus, and further reduced the serum PGE2 concentration. Together, these data indicates that L-Cit influenced the antioxidant defense, heat shock response and nitric oxide regeneration both under thermoneutral and HS conditions; and that L-Cit may be directly and/or indirectly involved in the central regulation of body temperature.

Project description:BACKGROUNDThe airways of obese asthmatics have been shown to be NO deficient, and this contributes to airway dysfunction and reduced response to inhaled corticosteroids. In cultured airway epithelial cells, L-citrulline, a precursor of L-arginine recycling and NO formation, has been shown to prevent asymmetric dimethyl arginine-mediated (ADMA-mediated) NO synthase (NOS2) uncoupling, restoring NO and reducing oxidative stress.METHODSIn a proof-of-concept, open-label pilot study in which participants were analyzed before and after treatment, we hypothesized that 15 g/d L-citrulline for 2 weeks would (a) increase the fractional excretion of NO (FeNO), (b) improve asthma control, and (c) improve lung function. To this end, we recruited obese (BMI >30) asthmatics on controller therapy, with a baseline FeNO of ≤30 ppb from the University of Colorado Medical Center and Duke University Health System.RESULTSA total of 41 subjects with an average FeNO of 17 ppb (95% CI, 15-19) and poorly controlled asthma (average asthma control questionnaire [ACQ] 1.5 [95% CI, 1.2-1.8]) completed the study. Compared with baseline, L-citrulline increased whereas ADMA and arginase concentration did not (values represent the mean Δ and 95% CI): plasma L-citrulline (190 μM, 84-297), plasma L-arginine (67 μM, 38-95), and plasma L-arginine/ADMA (ratio 117, 67-167). FeNO increased by 4.2 ppb (1.7-6.7 ppb); ACQ decreased by -0.46 (-0.67 to 0.27 points); the forced vital capacity and forced exhalation volume in 1 second, respectively, changed by 86 ml (10-161 ml) and 52 ml (-11 to 132 ml). In a secondary analysis, the greatest FEV1 increments occurred in those subjects with late-onset asthma (>12 years) (63 ml [95% CI, 1-137]), in females (80 ml [95% CI, 5-154]), with a greater change seen in late-onset females (100 ml, [95% CI, 2-177]). The changes in lung function or asthma control were not significantly associated with the changes before and after treatment in L-arginine/ADMA or FeNO.CONCLUSIONShort-term L-citrulline treatment improved asthma control and FeNO levels in obese asthmatics with low or normal FeNO. Larger FEV1 increments were observed in those with late-onset asthma and in females.TRIAL REGISTRATIONClinicalTrials.gov NCT01715844.FUNDINGNIH NHLBI R01 HL146542-01.

Project description:BackgroundThis study examined the efficacy of L-citrulline supplementation on the arginine/nitric oxide metabolism, and intestinal functions of broilers during arginine deficiency. A total of 288 day-old Arbor Acre broilers were randomly assigned to either an arginine deficient basal diet (NC diet), NC diet + 0.50% L-arginine (PC diet), or NC diet + 0.50% L-citrulline (NCL diet). Production performance was recorded, and at 21 days old, chickens were euthanized for tissue collection.ResultsThe dietary treatments did not affect the growth performance of broilers (P > 0.05), although NC diet increased the plasma alanine aminotransferase, urate, and several amino acids, except arginine (P < 0.05). In contrast, NCL diet elevated the arginine and ornithine concentration higher than NC diet, and it increased the plasma citrulline greater than the PC diet (P < 0.05). The nitric oxide concentration in the kidney and liver tissues, along with the plasma and liver eNOS activities were promoted by NCL diet higher than PC diet (P < 0.05). In the liver, the activities of arginase 1, ASS, and ASL, as well as, the gene expression of iNOS and OTC were induced by PC diet greater than NC diet (P < 0.05). In the kidney, the arginase 1, ASS and ASL enzymes were also increased by PC diet significantly higher than the NC and NCL diets. Comparatively, the kidney had higher abundance of nNOS, ASS, ARG2, and OTC genes than the liver tissue (P < 0.05). In addition, NCL diet upregulated (P < 0.05) the mRNA expression of intestinal nutrient transporters (EAAT3 and PEPT1), tight junction proteins (Claudin 1 and Occludin), and intestinal mucosal defense (MUC2 and pIgR). The intestinal morphology revealed that both PC and NCL diets improved (P < 0.05) the ileal VH/CD ratio and the jejunal VH and VH/CD ratio compared to the NC fed broilers.ConclusionThis study revealed that NCL diet supported arginine metabolism, nitric oxide synthesis, and promoted the intestinal function of broilers. Thus, L-citrulline may serve as a partial arginine replacement in broiler's diet without detrimental impacts on the performance, arginine metabolism and gut health of chickens.

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Central and peripheral effects of L-citrulline on thermal physiology and nitric oxide regeneration in broilers.

Publications

Central and peripheral effects of L-citrulline on thermal physiology and nitric oxide regeneration in broilers.

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