Liver Nitric Oxide Levels Research Articles

N-carbamylglutamate supplementation induces functional egg production in layers by modulating liver transcriptome profiles

Eggs rich in polyunsaturated fatty acids (PUFA), known as functional eggs, are animal products deemed beneficial to human health and possess high economic value. The production of functional eggs involves supplementing exogenous additives with the ability to regulate lipid metabolism. As N-Carbamylglutamate (NCG) serves as an endogenous arginine synthesizer, and arginine acts as the substrate for the formation of nitric oxide (NO), the biological function of NCG is partially mediated by NO. NO is a key regulatory molecule in lipid metabolism, suggesting that NCG may also have the ability to modulate lipid metabolism. In order to assess the capacity of NCG in regulating liver lipid metabolism and its potential application in producing functional eggs, we conducted a study to investigate the effects of dietary supplementation of NCG on production performance, serum, and liver NO levels, yolk fatty acid composition, and the liver transcriptome of layers. In this study, we utilized 30 layers of the Jinghong No.1 breed, all aged 45 wk. All the birds were randomly divided into 2 groups. Each group had 5 replicates, and each replicate had 3 birds. We provided them with different diets: one group received the basic diet, and the other group's diet was supplemented with 0.08% NCG. The experiment lasted for 14 wk. The results did not reveal any positive impact of NCG on production performance. However, NCG supplementation elevated NO levels in serum and liver, along with an increase in yolk PUFA, ω-3, and ω-6 fatty acids. Liver transcriptome analysis identified 124 upregulated differentially expressed genes (DEGs) and 43 downregulated DEGs due to NCG supplementation. Functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted 3 upregulated DEGs (CPT1A, MOGAT1, and CHKA) and 2 downregulated DEGs (FASN and ETNPPL) associated with lipid metabolism. Pathway enrichment analysis revealed that CPT1A was enriched in the AMPK signaling pathway and the PPAR signaling pathway, while FASN was enriched in the AMPK signaling pathway. Thus, CPT1A and FASN are potential functional genes related to lipid metabolism facilitated by NCG supplementation. In summary, our study suggests that NCG supplementation modulates liver lipid metabolism, leading to the production of functional eggs in layers.

Metformin alleviates sodium arsenite‐induced hepatotoxicity and glucose intolerance in mice by suppressing oxidative stress, inflammation, and apoptosis

BackgroundEpidemiological studies have shown that exposure to sodium arsenite (NaAsO2) causes diabetes and hepatotoxicity. Metformin (MET), an oral hypoglycemic agent, has long been used in diabetes therapy. In addition, MET has been shown to have hepatoprotective effects. In this study, we investigated the effects of MET on NaAsO2-induced hepatotoxicity and glucose intolerance in mice. MethodsMice were divided into four groups: Groups I and II received distilled water and NaAsO2 (10 mg/kg, p.o.) for five weeks, respectively. Groups III and IV were treated with NaAsO2 (10 mg/kg, p.o.) for three weeks, followed by MET (125 and 250 mg/kg, p.o.) for the last two weeks before NaAsO2. A glucose tolerance test was performed on day 35. The serum and tissue parameters were also evaluated. ResultsHistopathological examination revealed NaAsO2-induced liver and pancreatic damage. NaAsO2 caused hyperglycemia, glucose intolerance, and a significant increase in liver function enzymes. Administration of NaAsO2 significantly reduced hepatic superoxide dismutase, catalase, glutathione peroxidase, and total thiol levels and increased the content of reactive thiobarbituric acid substances. In addition, it led to an increase in liver nitric oxide levels and protein expression of tumor necrosis factor-α, nuclear factor kappa B, and cysteine-aspartic proteases-3. In contrast, treatment with MET (250 mg/kg) significantly improved NaAsO2-induced biochemical and histopathological changes. ConclusionOur findings suggest that the significant effects of MET against NaAsO2-induced hepatotoxicity and glucose intolerance may be exerted via the regulation of oxidative stress, followed by suppression of inflammation and apoptosis.

Dietary Inorganic Nitrate Protects Hepatic Ischemia-Reperfusion Injury Through NRF2-Mediated Antioxidative Stress.

Objectives: Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and liver transplantation and may cause hepatic impairment, resulting in acute liver dysfunction. Nitrate plays an important physiological regulatory role in the human body. Whether dietary nitrate could prevent HIRI is, however, unknown. Methods: A HIRI mouse model was established in that the blood supply to the median lobe and left lateral lobe was blocked for 60 min through the portal vein and related structures using an atraumatic clip. Sodium nitrate (4 mM) was administrated in advance through drinking water to compare the influence of sodium nitrate and normal water on HIRI. Results: Liver necrosis and injury aggravated after HIRI. The group treated with sodium nitrate showed the lowest activities of plasma aminotransferase and lactate dehydrogenase and improved outcomes in histological investigation and TUNEL assay. Mechanistically, sodium nitrate intake increased plasma and liver nitric oxide levels, upregulated nuclear factor erythroid 2-related factor 2 (NRF2)–related molecules to reduce malondialdehyde level, and increased the activities of antioxidant enzymes to modulate hepatic oxidative stress. Conclusions: Dietary inorganic nitrate could prevent HIRI, possibly by activating the NRF2 pathway and modulating oxidative stress. Our study provides a novel therapeutic compound that could potentially prevent HIRI during liver transplantation or hepatic surgery.

Effects of intravitreal injection of bevacizumab on nitric oxide levels.

This study aimed to determine the possible effects of single-dose intravitreal bevacizumab on nitric oxide (NO) levels in serum and remote organs and to reveal one of the possible mechanisms in the pathophysiology of hypertension. Thirty-eight adult New Zealand albino rabbits were divided into a control group (no injection was performed, killed on day 28 of the study), group 1 (killed on day 1 of the study), group 2 (killed on day 7 of the study), group 3 (killed on day 14 of the study), and group 4 (killed on day 28 of the study). The right eyes of the animals in groups 1-4 received an intravitreal single injection of 1.25 mg (0.05 ml) bevacizumab (Avastin), and their brain, heart, liver, kidney, and blood samples were collected. NO levels were evaluated in the serum and organ homogenates. Kidney tissues were assessed by electron microscopy. Serum, brain, kidney, and liver NO levels significantly decreased in groups 2, 3, and 4 as compared with the control group (P<0.05). In addition, heart NO levels significantly decreased in groups 3 and 4 compared with the control group (P<0.05). There were no electron microscopic changes in the kidneys of either group. This study demonstrated that single intravitreal injection of bevacizumab decreased NO levels in serum, brain, heart, liver, and kidneys. In addition, there were no electron microscopic changes in the kidneys.

Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine.

Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective.

Effect of manipulation of incubation temperature on fatty acid profiles and antioxidant enzyme activities in meat-type chicken embryos

Eggs (n = 1,800) obtained from Ross broiler breeders at 32 and 48 wk of age were incubated at either a constant temperature of 37.6°C throughout (T1), or the temperature was reduced for 6 h to 36.6°C each day during embryonic age (EA) 10 to 18 (T2). Yolk sac, liver, and brain fatty acid profiles and oxidant and antioxidant status of liver and brain were measured at EA 14, 19, and day of hatch (DOH). Fatty acid profiles of yolk sac, liver, and brain were influenced by age of breeder with significant breeder hen age × incubation temperature interactions. At EA 14, higher levels of 20:4n-6 and 22:6n-3 had been transferred from the yolk sac to T2 embryos from younger than older breeders, whereas for T1 and T2 embryos, yolk sac 20:4n-6 and 22.6n-3 values were similar for older breeders. Accumulation of 20:4n-6 and 22:6n-3 fatty acids in the liver of T1 and T2 embryos from younger breeders was similar; however, T2 embryos from older breeders had higher liver levels of 20:4n-6 and 22:6n-3 than T1 embryos. At EA 19, liver nitric oxide levels were higher for T2 embryos from younger breeders than those from breeders incubated at T1. Brain catalase levels of T2 embryos from younger breeders were higher than those from older breeders at DOH. Thus, changes in fatty acid profiles and catalase and nitric oxide production of brain and liver tissues resulting from 1°C lower incubation temperature from EA 10 to 18 reflect adaptive changes.

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The objective of this study was to determine the effects of metformin treatment and exercise intervention on lipid metabolism, nitric oxide (NO), nitric oxide synthase (NOS) and glucose levels in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats. Male wistar rats were used to conduct the study and they were divided into five groups of 8 rats in each. These groups are: Control group, diabetes group (STZ-NA), diabetes and metformin (DMet) group, diabetes and exercise (DE) group, and diabetes + exercise + metformin (DEMet) group. The STZ-NA induced diabetic rats were used as a model of type 2 diabetes. Metformin was orally administered to rats. For exercise intervention, rats were forced to run in a running wheel for 10 min each day (20 m/min/day). At the end of experimental period, blood glucose, glycated hemoglobin (HbA1c) levels, plasma lecithin:cholesterol acyltransferase (LCAT) levels, serum triglyceride (TG), cholesterol, high density lipoprotein (HDL), Apo A-I, NOS and liver NO levels were determined. Metformin caused beneficial changes in blood glucose, HbA1c levels, and HDL in type 2 diabetic rats. Both administration of metformin and exercise intervention independently caused beneficial changes in blood glucose. However, the surprising result found was that exercise intervention did not optimize the result of metformin treatment. The other finding of this study was that exercise intervention increased cholesterol and NOS level but exercise combined with metformin was not better than exercise alone. Thus, it appears from the present study that metformin and exercise combination has no effect. Key words: Diabetes, exercise, lecithin:cholesterol acyltransferase (LCAT), metformin, nitric oxide synthase.

Antibacterial peptide PR-39 affects local nitric oxide and preserves tissue oxygenation in the liver during septic shock

The effects of the antibacterial peptide PR-39 on nitric oxide (NO) and liver oxygenation (pO 2) in a mouse model of endotoxaemia have been explored. In vivo electron paramagnetic resonance (EPR) spectroscopy was used to make direct measurements of liver NO and pO 2. Measurements of pO 2 were made at two different anatomical locations within hepatic tissue to assess effects on blood supply (hence oxygen supply) and lobule oxygenation; selectively from the liver sinusoids or an average pO 2 across the liver lobule. PR-39 induced elevated levels of liver NO at 6 h following injection of lipopolysaccharide (LPS) as a result of increased iNOS expression in liver, but had no effect on eNOS or circulatory NO metabolites. Sinusoidal oxygenation was preserved, and pO 2 across the hepatic tissue bed improved with PR-39 treatment. We propose that the beneficial effects of PR-39 on liver in this septic model were mediated by increased levels of local NO and preservation of oxygen supply to the liver sinusoids.

ESR measurement of endogenous nitric oxide in liver and blood of mice subjected to hepatic ischemia-reperfusion

To examine the role of nitric oxide (NO) in liver ischemia-reperfusion injuries, electron spin resonance (ESR) measurements were employed to directly detect NO in the liver and blood of mice subjected to liver ischemia-reperfusion. We used an NO trapping and accumulating reagent, N-(dithiocarboxy)sarcosine/Fe 2+(DTCS/Fe) that specifically binds to NO to form stable NO adduct, (DTCS)/Fe-NO. The DTCS/Fe-NO adduct is detectable by ESR spectrometry at room temperature, giving rise to a characteristic triplet spectrum. The (DTCS)/Fe-NO contents in liver and blood decreased during ischemia, and still more decreased at the early reflow phase. Then, 12 h after reflow onset, the adduct content increased approximately 1.5-fold in the liver and 2.5-fold in the blood compared to that in a non-ischemia group. The fluctuation of liver NO levels may have resulted from a lack of oxygen during ischemia and the scavenging of superoxide anions during the early reflow phase. Therefore, NO levels would result in decline, then a subsequent boost in NO levels as cells respond to the reperfusion-induced damage. Blood endotoxin concentration and serum aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were significantly higher in the liver ischemia-reperfused group than in the sham-operated group. Pretreatment with N G-mono- N-methyl- l-arginine, an NO synthase inhibitor resulted in decreased NO levels to an undetectable level, all the more increased lipid peroxide contents in liver, and the amelioration of hepatic injury induced by 60 min of liver ischemia followed by 60 min of reperfusion. From these results, NO was interpreted to protect against injuries in part to brake the progression of the free radical chain reaction.