Metabolic studies reveal that ruminal microbes of adult steers do not degrade rumen-protected or unprotected L-citrulline

Gilbreath, Kyler R; Nawaratna, Gayan; Wickersham, T.A.; Satterfield, M. Carey; Bazer, Fuller W

doi:10.1093/jas/skz370

Cited by 20 publications

(19 citation statements)

References 38 publications

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“…Further, cells and tissues which have high arginase activity contribute to the relatively short biological halflife of L-arginine in mammals, and intestinal arginase, specifically, inhibits the availability of orally provided supplemental L-arginine in humans (Castillo et al 1993, Wu et al 2007. L-citrulline is a neutral amino acid and is an effective precursor for arginine synthesis in humans, pigs, ruminants, and rodents (Gilbreath et al 2020). In pregnant sheep, the half-life of L-citrulline is twice that of L-arginine and was more effective in sustaining high concentrations of arginine in both the maternal and fetal circulations, as well as ornithine in the fetal circulation (Lassala et al 2009).…”

Section: Nutritional Strategies To Improve Placental Growth and Functionmentioning

confidence: 99%

Placental adaptation to maternal malnutrition

et al. 2021

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Maternal malnutrition gives rise to both short- and long-term consequences for the survival and health of the offspring. As the intermediary between mother and fetus, the placenta has the potential to interpret environmental signals, such as nutrient availability, and adapt to support fetal growth and development. While this potential is present, it is clear that at times, placental adaptation fails to occur resulting in poor pregnancy outcomes. This review will focus on placental responses to maternal undernutrition related to changes in placental vascularization and hemodynamics and placental nutrient transport systems across species. While much of the available literature describes placental responses that result in poor fetal outcomes, novel models have been developed to utilize the inherent variation in fetal weight when dams are nutrient restricted to identify placental adaptations that result in normal weight offspring. Detailed analyses of the spectrum of placental responses to maternal malnutrition point to alternations in placental histoarchitectural and vascular development, amino acid and lipid transport mechanisms, and modulation of immune related factors. Dietary supplementation with select nutrients, such as arginine, have the potential to improve placental growth and function through a variety of mechanisms including stimulating cell proliferation, protein synthesis, angiogenesis, vasodilation, and gene regulation. Improved understanding of placental responses to environmental cues is necessary to develop diagnostic and intervention strategies to improve pregnancy outcomes.

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Section: Nutritional Strategies To Improve Placental Growth and Functionmentioning

confidence: 99%

Placental adaptation to maternal malnutrition

et al. 2021

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“…All CITM ewes received the same dose of 7.29 g of citrulline from d 86 of gestation to parturition, which provided less than 5% of their daily nitrogen intake. This dose Citrulline was chosen over arginine due to the extremely high degradation of arginine by rumen bacteria ( Chalupa, 1976 ; Gilbreath et al, 2020b ). Citrulline dose was delivered as an individual, oral drench (10.935 g citrulline-malate 2:1/35 mL ultrapure water) prior to feeding each morning.…”

Section: Methodsmentioning

confidence: 99%

“…Citrulline (Cit) may be a viable alternative to arginine, as it is part of the urea cycle and can be converted into Arg ( Ah Mew et al, 2003 ). Citrulline has been confirmed to survive rumen degradation in vitro and in vivo with sheep ( Gilbreath et al, 2020a ) and cattle ( Gilbreath et al, 2020b ). Additionally, Cit has been shown to be more effective at elevating Arg concentrations when administered intravenously ( Lassala et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of oral citrulline administration as a mitigation strategy for fescue toxicosis in sheep

Greene

Klotz²,

Goodman

et al. 2020

Translational Animal Science

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Gestating ewes consuming ergot alkaloids, from endophyte-infected (E+) tall fescue seed, suffer from intrauterine growth restriction and produce smaller lambs. Arginine (Arg) supplementation has been shown to increase birth weight and oral citrulline (Cit) administration is reported to increase arginine concentrations. Two experiments were conducted to: 1) evaluate if oral supplementation with Cit or water, to ewes consuming E+ fescue seed, increases lamb birth weight and 2) determine the effectiveness of Cit and citrulline:malate as an oral drench and elevating circulating levels of Cit to determine levels and dose frequency. In Experiment 1, gestating Suffolk ewes (n = 10) were assigned to one of two treatments [oral drench of citrulline-malate 2:1 (CITM; 81 mg/kg/d of citrulline) or water (TOX)] to start on d 86 of gestation and continued until parturition. Ewes on CITM treatment had decreased (P < 0.05) plasma Arg and Cit concentrations during gestation. At birth, lambs from CITM ewes had reduced (P < 0.05) crude fat and total fat but did not differ (P > 0.05) in birth weight from lambs born to TOX ewes. In Experiment 2, non-pregnant Suffolk ewes (n = 3) were assigned to either oral citrulline (CIT; 81 mg/kg/d), citrulline-malate 2:1 (CITM; 81 mg/kg/d of citrulline), or water (CON) drench in a Latin Square design for a treatment period of 4 d with a washout period of 3 d. On d 4, blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 18 h post drench. Oral drenching of CIT and CITM increased (P < 0.0001) Cit concentrations within 2 h and levels remained elevated for 6 h. Apparent half-life of elimination for CIT and CITM were 8.484 h and 10.392 h, respectively. Our results show that lamb birth weight was not altered with a single oral drench of citrulline-malate; however, lamb body composition was altered. The level and frequency of citrulline dosing may need to be greater in order to observe consistent elevation of Cit/Arg concentrations to determine its effectiveness in mitigating fescue toxicosis.

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“…This dose was determined based on previous studies using arginine supplementation (Lassala et al, 2009;Lassala et al, 2010Lassala et al, , 2011Satter eld et al, 2013;Wu et al, 2016). Citrulline was chosen over arginine due to the extremely high degradation of arginine by rumen bacteria (Chalupa, 1976;Gilbreath et al, 2020b).…”

Section: Methodsmentioning

confidence: 99%

“…Citrulline (Cit) may be a viable alternative to arginine, as it is part of the urea cycle and can be bio-transformed into Arg (Ah Mew et al, 2003). Citrulline has been con rmed to survive rumen degradation in vitro and in vivo with sheep (Gilbreath et al, 2020a) and with cattle (Gilbreath et al, 2020b). Additionally, Cit has been shown to be more effective at raising Arg concentrations when administered intravenously (Lassala et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Use of Oral Citrulline Administration as a Mitigation Strategy for Fescue Toxicosis in Sheep

Greene

Klotz²,

Goodman

et al. 2020

Preprint

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Background: Gestating ewes consuming ergot alkaloids, from endophyte-infected (E+) tall fescue seed, produce smaller lambs suffering from intrauterine growth restriction. Arginine (Arg) supplementation has been shown to increase birth weight and oral citrulline (Cit) administration is reported to increase arginine concentrations. Two experiments were conducted to: 1) evaluate if oral supplementation with Cit or water, to ewes consuming E+ fescue seed, increases lamb birth weight and 2) determine the effectiveness of Cit and citrulline:malate as an oral drench in elevating circulating levels of Cit to determine dosing levels and frequency of dose. In Experiment 1, gestating Suffolk ewes (n = 10) were assigned to one of two treatments [oral drench of citrulline-malate 2:1 (CITM; 81 mg/kg/d of citrulline) or water (TOX)] to start on d 86 of gestation. In Experiment 2, non-pregnant Suffolk ewes (n = 3) were assigned to either oral citrulline (CIT; 81 mg/kg/d), citrulline-malate 2:1 (CITM; 81 mg/kg/d of citrulline), or water (CON) drench in a Latin Square design for a treatment period of 4 d with a washout period of 3 d. On d 4, blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 18 h post drench.Results:Expt 1: Ewes on CITM treatment had decreased (P < 0.05) plasma Arg and Cit concentrations during gestation. At birth, lambs from CITM ewes had reduced (P < 0.05) crude fat and total fat but did not differ (P > 0.05) in birth weight from lambs born to TOX ewes. Expt 2: Oral drenching of CIT and CITM increased (P < 0.0001) Cit concentrations within 2 h and levels remained elevated for 8 h. Apparent half-life of elimination for CIT and CITM were 8.484 h and 10.392 h respectively.Conclusions: Our results show that lamb birth weight was not altered with a single oral drench of citrulline-malate; however, lamb body composition was altered. The level and frequency of citrulline dosing may need to be greater in order to observe consistent elevation of Cit/Arg concentrations to determine its effectiveness in mitigating fescue toxicosis.

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Metabolic studies reveal that ruminal microbes of adult steers do not degrade rumen-protected or unprotected L-citrulline

Cited by 20 publications

References 38 publications

Placental adaptation to maternal malnutrition

Placental adaptation to maternal malnutrition

Evaluation of oral citrulline administration as a mitigation strategy for fescue toxicosis in sheep

Use of Oral Citrulline Administration as a Mitigation Strategy for Fescue Toxicosis in Sheep

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