Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate...Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate the effects of in ovo feeding(IOF)of L-arginine(Arg)on growth,intestinal development,intestinal microbiota and metabolism.The treatments included the non-injected control,saline-injected control,and saline containing 2,6,or 10 mg Arg groups.Results:IOF Arg increased early intestinal index and villus height,and enhanced uptake of residual yolk lipid,contributing to subsequent improvement in the early growth performance of chicks.Prenatal Arg supplementation also increased the early microbialα-diversity,the relative abundance of Lactobacillales and Clostridiales,and decreased the relative abundance of Proteobacteria of cecum in chicks.Furthermore,the shift of cecal microbiota composition and the colonization of potential probiotics were accelerated by IOF of Arg.Simultaneously,metabolomics showed that metabolisms of galactose,taurine-conjugated bile acids and lipids were modulated to direct more energy and nutrients towards rapid growth of intestine at the beginning of post-hatch when embryos received IOF of Arg.Conclusions:Prenatal Arg supplementation showed beneficial effects on the early intestinal development,cecal microbiota and host metabolism of layer chicks,contributing to subsequent improvement in the early growth performance.These findings provide new insight into the role of IOF of Arg in the establishment of the gut microbiota of newly-hatched layer chicks,and can expand our fundamental knowledge about prenatal nutrition,early bacterial colonization and intestinal development in neonate.展开更多
Objective In Corynebacterium crenatum,the adjacent D311 and D312 of N-acetyl-L-glutamate kinase(NAGK),as a key rate-limiting enzyme of L-arginine biosynthesis under substrate regulatory control by arginine,were initia...Objective In Corynebacterium crenatum,the adjacent D311 and D312 of N-acetyl-L-glutamate kinase(NAGK),as a key rate-limiting enzyme of L-arginine biosynthesis under substrate regulatory control by arginine,were initially replaced with two arginine residues to investigate the L-arginine feedback inhibition for NAGK.Methods NAGK enzyme expression was evaluated using a plasmid-based method.Homologous recombination was employed to eliminate the pro B.Results The IC50 and enzyme activity of NAGK M4,in which the D311 R and D312 R amino acid substitutions were combined with the previously reported E19 R and H26 E substitutions,were 3.7-fold and 14.6% higher,respectively,than those of the wild-type NAGK.NAGK M4 was successfully introduced into the C.crenatum MT genome without any genetic markers;the L-arginine yield of C.crenatum MT-M4 was 26.2% higher than that of C.crenatum MT.To further improve upon the L-arginine yield,we constructed the mutant C.crenatum MT-M4 ?pro B.The optimum concentration of L-proline was also investigated in order to determine its contribution to L-arginine yield.After L-proline was added to the medium at 10 mmol/L,the L-arginine yield reached 16.5 g/L after 108 h of shake-flask fermentation,approximately 70.1% higher than the yield attained using C.crenatum MT.Conclusion Feedback inhibition of L-arginine on NAGK in C.crenatum is clearly alleviated by the M4 mutation of NAGK,and deletion of the pro B in C.crenatum from MT to M4 results in a significant increase in arginine production.展开更多
Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase...Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential tox- icity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics.展开更多
BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary ...BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.展开更多
BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilat...BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilator agentformed when L-arginine ( L-Arg) is converted to L-citrul-line by the action of NO synthase (NOS), and plays a ma-jor role in microcirculatory changes. We therefore investi-gated the effect of L-Arg on reperfusion injury followingpancreaticoduodenal transplantation in rats.METHODS: The homologous male Wistar rat model ofheterotopic total pancreaticoduodenal transplantation wasused. The L-Arg-treated rats received the intravenous in-jection of L-Arg 5 minutes before and after reperfusion at adose of 200 mg/kg while the N-Nitro-L-arginine methyl es-ter (L-NAME) -treated rats at a dose of 10 mg/kg. Theamount of NO in the pancreas graft was measured. Serumconcentration of cytokine-induced neutrophil chemoattrac-tant ( CINC) was determined by enzyme-linked immu-nosorbant assay, the expression of CINC mRNA was detect-ed by Northern blot assay in the pancreas graft, and the ac-tivity of myeloperoxidase (MPO) was measured. Histolo-gical examination was performed.RESULTS: The amount of NO was higher in the L-Arggroup than in the control group, while it was lower in theL-NAME group than in the control group (P <0.05). Thepeak of serum CINC concentration occurred 3 hours afterreperfusion with the difference among the groups being sig-nificant. The expression peak of CINC mRNA in the pan-creas graft occurred 3 hours after reperfusion. The expres-sion level in the L-Arg group (7.66 ± 1.53 μg/L) was lowerthan in the control group (26.31±2.01 μg/L), while in theL-NAME group (34.18 ±3.12 μg/L) it was higher than thatin the control group (P <0. 05). The activity of MPO inthe L-Arg group was obviously decreasd as compared within the other groups. The pancreas inflammation was ame-liorated when L-Arg was administered, whereas the panc-reas damage was aggravated when L-NAME was adminis-tered.CONCLUSIONS: L-Arg can increase the amount of NOand inhibit the elevation of CINC, the CINC mRNA ex-pression and early neutrophil accumulation in the pancreas.NO has protective effects on ischemia/reperfusion injury inpancreaticoduodenal transplantation.展开更多
Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposi...Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.展开更多
In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various proc...In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.展开更多
Aim: To examine the effect of L-arginine, the substrate of nitric oxide (NO) synthase, on reproductive function ofmale rats. Methods: Male rats were gavaged with either L-arginine (100 or 200 mg·kg^(-1)·d^(-...Aim: To examine the effect of L-arginine, the substrate of nitric oxide (NO) synthase, on reproductive function ofmale rats. Methods: Male rats were gavaged with either L-arginine (100 or 200 mg·kg^(-1)·d^(-1)), D-arginine (200mg·kg^(-1)·d^(-1)) or vehicle (0.9% NaCl) for seven consecutive days. Their sexual behaviour and fertility were evaluat-ed using receptive females. Results: L-arginine (200 mg/kg) had no significant effect on sexual competence (interms of sexual arousal, libido, sexual vigour and sexual performance). In mating experiments, the higher dose of L-arginine effectively and reversibly inhibited fertility, whilst the lower dose and the inactive stereoisomer D-arginine hadno significant effect. The antifertility effect caused by L-arginine was due to a profound elevation in the preimplantationloss mediated possibly by impairment in epididymal sperm maturation, hyperactivated sperm motility and sperm capaci-tation. Conclusion: Elevated NO production may be detrimental to male fertility.展开更多
AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreati...AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation.展开更多
AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes...AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.展开更多
A 2 × 2 factorial arrangement was designed to test effects of supplementation of a low (L, 75 mg/kg BW) vs. high (H, 150 mg/kg BW) L-arginine given at early (first 56 days) vs. late (last 56 days) pregnancy on ma...A 2 × 2 factorial arrangement was designed to test effects of supplementation of a low (L, 75 mg/kg BW) vs. high (H, 150 mg/kg BW) L-arginine given at early (first 56 days) vs. late (last 56 days) pregnancy on maternal hormones and neonatal traits. Thirty Najdi pregnant ewes were randomly allocated into 6 groups. Ewes in G1 and G2 served as controls (C), given 50 ml saline at either early (CE) or late (CL) pregnancy, respectively. G3 and G4 ewes in early pregnancy received low (LE) and high L-arginine (HE), respectively. G5 and G6 ewes in late pregnancy received low (LL) and high (HL) L-arginine, respectively. A weekly blood sample was collected from initiation of the treatment till parturition. Serum growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, progesterone (P4) and estradiol 17 β (E2) profiles were determined. Neonatal traits were also determined. Insulin was higher (P 0.05). Lamb survival rates at birth in LE ewes were highest (100%) compared to other treatments. In conclusion, supplementing pregnant ewes with low dosage of L-arginine at early stage of gestation increased lamb birth weight and survival, and improved maternal health.展开更多
AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginin...AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 × 2.5 g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose of α,β-amyrin (10, 30 and 100 mg/kg),methylprednisolone (30 mg/kg) and vehicle (3% Tween 80). A saline (0.9% NaCl) treated group served as a normal control. Efficacy was assessed at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Tissue histology and the immunoreactivity for TNF-α and inducible nitric oxide synthetase (iNOS) were performed. RESULTS: α,β-amyrin and methylprednisolone treatments significantly (P < 0.05) attenuated the L-arginine-induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6, as compared to the vehicle control. Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were signifi cantly lower. Histological f indings and TNF-α and iNOS immunostaining further confirmed the amelioration of pancreatic injury by α,β-amyrin. CONCLUSION: α,β-amyrin has the potential to combat acute pancreatitis by acting as an anti-in? ammatory and antioxidant agent.展开更多
The enthalpies of mixing of L-arginine with 2,2,2-trifluoroethanol and their respective enthalpies of dilu- tion in aqueous solutions at 298.15, 303.15 and 310.15 K were determined as a function of the mole fraction b...The enthalpies of mixing of L-arginine with 2,2,2-trifluoroethanol and their respective enthalpies of dilu- tion in aqueous solutions at 298.15, 303.15 and 310.15 K were determined as a function of the mole fraction by flow microcalorimetric measurement. These experimental results were analyzed to obtain heterotactic enthalpic interaction coeffieients(hxy , hxy , hxy) according to the McMillan-Mayer theory. The hxy coefficients between L-arginine molecule studied and 2,2,2-trifluoroethanol molecule in aqueous solutions at 298.15, 303.15 and 310.15 K were found to be all negative. The results were discussed in terms of solute-solute interaction and solute-solvent interaction.展开更多
The influence of L-arginine on endothelial nitric oxide synthase (eNOS) and cyclooxygenase 2 (COX2) was observed in experimental pulmonary thromboembolism and the action mechanism on pulmonary thromboembolism was ...The influence of L-arginine on endothelial nitric oxide synthase (eNOS) and cyclooxygenase 2 (COX2) was observed in experimental pulmonary thromboembolism and the action mechanism on pulmonary thromboembolism was explored. Wistar rats were randomly divided into control group, model group and treatment group. Pulmonary thromboembolism models were established by auto-blood back transfusion, and L-Arg 100 mg/kg was intraperitoneally injected after successful model preparation. The animals were sacrificed at 3 h, 1 day, 3 days and 7 days after embolism. Plasma NO, TXB2 and 6-Keto-PGF1 α were detected. The expression of eNOS and COX2 protein and mRNA in pulmonary tissues was detected by immunohistochemistry and RT-PCR respectively. The results showed that pulmonary thrombosis could be seen post pulmonary embolism and inflammatory reaction was significant. Plasma NO was decreased (P〈0.01), and the levels of TXB2, 6-Keto-PGF1α and T/P ratio were all elevated. The expression of eNOS protein and mRNA in the pulmonary tissue was down-regulated (P〈0.05), while that of COX2 protein and mRNA was upregulated (P〈0.01). In treatment group, the level of NO was increased, the levels of TXB2 and T/P ratio were decreased, but the level of 6-Keto-PGF1 α was increased. The expression of eNOS protein and mRNA in pulmonary tissue was upregulated (P〈0.05), while that of COX2 protein and mRNA was down-regulated (P〈0.05). In conclusion, L-arginine can educe the role of pulmonary tissue protection through up-regulating the expression of intra-pulmonary NOS and down -regulating COX2 in pulmonary thromboembolism.展开更多
基金This study was supported by National Key R&D Program of China(2017YFD0500500)the earmarked fund for Modern Agro-industry Technology Research System(CARS-40-K12)+1 种基金Beijing Innovation Consortium of Agriculture Research System(BAIC04–2018)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences.
文摘Background:Prenatal nutrition is crucial for embryonic development and neonatal growth,and has the potential to be a main determinant of life-long health.In the present study,we used a layer chick model to investigate the effects of in ovo feeding(IOF)of L-arginine(Arg)on growth,intestinal development,intestinal microbiota and metabolism.The treatments included the non-injected control,saline-injected control,and saline containing 2,6,or 10 mg Arg groups.Results:IOF Arg increased early intestinal index and villus height,and enhanced uptake of residual yolk lipid,contributing to subsequent improvement in the early growth performance of chicks.Prenatal Arg supplementation also increased the early microbialα-diversity,the relative abundance of Lactobacillales and Clostridiales,and decreased the relative abundance of Proteobacteria of cecum in chicks.Furthermore,the shift of cecal microbiota composition and the colonization of potential probiotics were accelerated by IOF of Arg.Simultaneously,metabolomics showed that metabolisms of galactose,taurine-conjugated bile acids and lipids were modulated to direct more energy and nutrients towards rapid growth of intestine at the beginning of post-hatch when embryos received IOF of Arg.Conclusions:Prenatal Arg supplementation showed beneficial effects on the early intestinal development,cecal microbiota and host metabolism of layer chicks,contributing to subsequent improvement in the early growth performance.These findings provide new insight into the role of IOF of Arg in the establishment of the gut microbiota of newly-hatched layer chicks,and can expand our fundamental knowledge about prenatal nutrition,early bacterial colonization and intestinal development in neonate.
基金supported by Natural Science Foundation of China,No.31360219 and No.30960012the Open Project Program of Key Laboratory of Functional Small Organic Molecule,Ministry of Education,Jiangxi Normal University(No.KLFS-KF-201414)
文摘Objective In Corynebacterium crenatum,the adjacent D311 and D312 of N-acetyl-L-glutamate kinase(NAGK),as a key rate-limiting enzyme of L-arginine biosynthesis under substrate regulatory control by arginine,were initially replaced with two arginine residues to investigate the L-arginine feedback inhibition for NAGK.Methods NAGK enzyme expression was evaluated using a plasmid-based method.Homologous recombination was employed to eliminate the pro B.Results The IC50 and enzyme activity of NAGK M4,in which the D311 R and D312 R amino acid substitutions were combined with the previously reported E19 R and H26 E substitutions,were 3.7-fold and 14.6% higher,respectively,than those of the wild-type NAGK.NAGK M4 was successfully introduced into the C.crenatum MT genome without any genetic markers;the L-arginine yield of C.crenatum MT-M4 was 26.2% higher than that of C.crenatum MT.To further improve upon the L-arginine yield,we constructed the mutant C.crenatum MT-M4 ?pro B.The optimum concentration of L-proline was also investigated in order to determine its contribution to L-arginine yield.After L-proline was added to the medium at 10 mmol/L,the L-arginine yield reached 16.5 g/L after 108 h of shake-flask fermentation,approximately 70.1% higher than the yield attained using C.crenatum MT.Conclusion Feedback inhibition of L-arginine on NAGK in C.crenatum is clearly alleviated by the M4 mutation of NAGK,and deletion of the pro B in C.crenatum from MT to M4 results in a significant increase in arginine production.
基金supported by the following grants:National Institute of Environmental Health Sciences funded training program in Environmental Health Sciences (No.T32 ES007058-33) to Jennifer M.Bratt,CTSC K12 Award (No.UL1RR024146)KL2RR024144 to Amir A.Zekithe American Asthma Foundation to Nicholas J.Kenyon.
文摘Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential tox- icity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics.
基金a grant from the Science & Technology Development Foundation of Guangdong Health Bureau(No.2006345).
文摘BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.
基金This study was supported by a grant from foundation of Liaoning ProvincialKey Projects ( No. 0025001 ), China.
文摘BACKGROUND: Post-transplantation pancreatitis andgraft thrombosis are two major complications of pancreastrans-plantation that contribute to morbidity, mortality, andgraft loss. Nitric oxide (NO) is a potent vasodilator agentformed when L-arginine ( L-Arg) is converted to L-citrul-line by the action of NO synthase (NOS), and plays a ma-jor role in microcirculatory changes. We therefore investi-gated the effect of L-Arg on reperfusion injury followingpancreaticoduodenal transplantation in rats.METHODS: The homologous male Wistar rat model ofheterotopic total pancreaticoduodenal transplantation wasused. The L-Arg-treated rats received the intravenous in-jection of L-Arg 5 minutes before and after reperfusion at adose of 200 mg/kg while the N-Nitro-L-arginine methyl es-ter (L-NAME) -treated rats at a dose of 10 mg/kg. Theamount of NO in the pancreas graft was measured. Serumconcentration of cytokine-induced neutrophil chemoattrac-tant ( CINC) was determined by enzyme-linked immu-nosorbant assay, the expression of CINC mRNA was detect-ed by Northern blot assay in the pancreas graft, and the ac-tivity of myeloperoxidase (MPO) was measured. Histolo-gical examination was performed.RESULTS: The amount of NO was higher in the L-Arggroup than in the control group, while it was lower in theL-NAME group than in the control group (P <0.05). Thepeak of serum CINC concentration occurred 3 hours afterreperfusion with the difference among the groups being sig-nificant. The expression peak of CINC mRNA in the pan-creas graft occurred 3 hours after reperfusion. The expres-sion level in the L-Arg group (7.66 ± 1.53 μg/L) was lowerthan in the control group (26.31±2.01 μg/L), while in theL-NAME group (34.18 ±3.12 μg/L) it was higher than thatin the control group (P <0. 05). The activity of MPO inthe L-Arg group was obviously decreasd as compared within the other groups. The pancreas inflammation was ame-liorated when L-Arg was administered, whereas the panc-reas damage was aggravated when L-NAME was adminis-tered.CONCLUSIONS: L-Arg can increase the amount of NOand inhibit the elevation of CINC, the CINC mRNA ex-pression and early neutrophil accumulation in the pancreas.NO has protective effects on ischemia/reperfusion injury inpancreaticoduodenal transplantation.
基金Supported by the National Natural Science Foundation of China (No. 31625025, 31572410, 31572412, 31272450, 31272451)the “111” Project (B16044)。
文摘Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.
基金The Finnish Cultural Foundation and The Emil Aaltonen Foundation for the financial support.
文摘In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was developed.As such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or tuberculosis.Various processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and excipients.The formulations were evaluated using several analytical methods to assess suitability for further investigation.Several batches had enhanced in vitro aerolization properties.Significant future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.
文摘Aim: To examine the effect of L-arginine, the substrate of nitric oxide (NO) synthase, on reproductive function ofmale rats. Methods: Male rats were gavaged with either L-arginine (100 or 200 mg·kg^(-1)·d^(-1)), D-arginine (200mg·kg^(-1)·d^(-1)) or vehicle (0.9% NaCl) for seven consecutive days. Their sexual behaviour and fertility were evaluat-ed using receptive females. Results: L-arginine (200 mg/kg) had no significant effect on sexual competence (interms of sexual arousal, libido, sexual vigour and sexual performance). In mating experiments, the higher dose of L-arginine effectively and reversibly inhibited fertility, whilst the lower dose and the inactive stereoisomer D-arginine hadno significant effect. The antifertility effect caused by L-arginine was due to a profound elevation in the preimplantationloss mediated possibly by impairment in epididymal sperm maturation, hyperactivated sperm motility and sperm capaci-tation. Conclusion: Elevated NO production may be detrimental to male fertility.
文摘AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation.
文摘AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.
文摘A 2 × 2 factorial arrangement was designed to test effects of supplementation of a low (L, 75 mg/kg BW) vs. high (H, 150 mg/kg BW) L-arginine given at early (first 56 days) vs. late (last 56 days) pregnancy on maternal hormones and neonatal traits. Thirty Najdi pregnant ewes were randomly allocated into 6 groups. Ewes in G1 and G2 served as controls (C), given 50 ml saline at either early (CE) or late (CL) pregnancy, respectively. G3 and G4 ewes in early pregnancy received low (LE) and high L-arginine (HE), respectively. G5 and G6 ewes in late pregnancy received low (LL) and high (HL) L-arginine, respectively. A weekly blood sample was collected from initiation of the treatment till parturition. Serum growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin, progesterone (P4) and estradiol 17 β (E2) profiles were determined. Neonatal traits were also determined. Insulin was higher (P 0.05). Lamb survival rates at birth in LE ewes were highest (100%) compared to other treatments. In conclusion, supplementing pregnant ewes with low dosage of L-arginine at early stage of gestation increased lamb birth weight and survival, and improved maternal health.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil
文摘AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 × 2.5 g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose of α,β-amyrin (10, 30 and 100 mg/kg),methylprednisolone (30 mg/kg) and vehicle (3% Tween 80). A saline (0.9% NaCl) treated group served as a normal control. Efficacy was assessed at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Tissue histology and the immunoreactivity for TNF-α and inducible nitric oxide synthetase (iNOS) were performed. RESULTS: α,β-amyrin and methylprednisolone treatments significantly (P < 0.05) attenuated the L-arginine-induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6, as compared to the vehicle control. Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were signifi cantly lower. Histological f indings and TNF-α and iNOS immunostaining further confirmed the amelioration of pancreatic injury by α,β-amyrin. CONCLUSION: α,β-amyrin has the potential to combat acute pancreatitis by acting as an anti-in? ammatory and antioxidant agent.
基金Supported by the Natural Scientific Foundation of Shandong Province, China(NoZ2007B03)the Doctoral Fund of the Ministry of Education of China(New Teachers Fund)(No070422047)
文摘The enthalpies of mixing of L-arginine with 2,2,2-trifluoroethanol and their respective enthalpies of dilu- tion in aqueous solutions at 298.15, 303.15 and 310.15 K were determined as a function of the mole fraction by flow microcalorimetric measurement. These experimental results were analyzed to obtain heterotactic enthalpic interaction coeffieients(hxy , hxy , hxy) according to the McMillan-Mayer theory. The hxy coefficients between L-arginine molecule studied and 2,2,2-trifluoroethanol molecule in aqueous solutions at 298.15, 303.15 and 310.15 K were found to be all negative. The results were discussed in terms of solute-solute interaction and solute-solvent interaction.
文摘The influence of L-arginine on endothelial nitric oxide synthase (eNOS) and cyclooxygenase 2 (COX2) was observed in experimental pulmonary thromboembolism and the action mechanism on pulmonary thromboembolism was explored. Wistar rats were randomly divided into control group, model group and treatment group. Pulmonary thromboembolism models were established by auto-blood back transfusion, and L-Arg 100 mg/kg was intraperitoneally injected after successful model preparation. The animals were sacrificed at 3 h, 1 day, 3 days and 7 days after embolism. Plasma NO, TXB2 and 6-Keto-PGF1 α were detected. The expression of eNOS and COX2 protein and mRNA in pulmonary tissues was detected by immunohistochemistry and RT-PCR respectively. The results showed that pulmonary thrombosis could be seen post pulmonary embolism and inflammatory reaction was significant. Plasma NO was decreased (P〈0.01), and the levels of TXB2, 6-Keto-PGF1α and T/P ratio were all elevated. The expression of eNOS protein and mRNA in the pulmonary tissue was down-regulated (P〈0.05), while that of COX2 protein and mRNA was upregulated (P〈0.01). In treatment group, the level of NO was increased, the levels of TXB2 and T/P ratio were decreased, but the level of 6-Keto-PGF1 α was increased. The expression of eNOS protein and mRNA in pulmonary tissue was upregulated (P〈0.05), while that of COX2 protein and mRNA was down-regulated (P〈0.05). In conclusion, L-arginine can educe the role of pulmonary tissue protection through up-regulating the expression of intra-pulmonary NOS and down -regulating COX2 in pulmonary thromboembolism.